gene

LRRK2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about LRRK2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

2625Connections

9Hypotheses

8Analyses

50Outgoing

50Incoming

2Experiments

9Debates

Summary

A gene referenced in 1 knowledge graph relationship. Key connections: inhibits GCase_trafficking (mechanism).

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AI-generated illustration · click image to enlarge

Regenerate portrait ↻

🧬 Gene Info

Gene Symbol	LRRK2
Full Name	Leucine Rich Repeat Kinase 2
Chromosome	12q12
Protein Type	Protein
Subcellular Localization	Cytoplasmic vesicle, Perikaryon, Golgi apparatus membrane, Cell projection, axon, Cell projection, dendrite, Endoplasmic
Amino Acids	2527 aa
Pathways	MAPK
UniProt ID	Search UniProt
GeneCards	LRRK2
Human Protein Atlas	LRRK2
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	BIIB094, BIIB122, Cigarette Smoking, DNL201, Environmental Toxicants, levodopa
Interactions	6-OHDA, ACETYLCHOLINE, ACHE, Actin, AD, AKT
SciDEX Hypotheses	G2019S primarily raises baseline LRRK2 kinase acti Therapeutic Window Exists Because Amplified Signal LRRK2 Volume Sensor Hijacking Drives Metabolic Dys (+3 more)
KG Connections	2622 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — LRRK2 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

6VP6 — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q5S007 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    LRRK2["LRRK2"] -->|"causes"| PD["PD"]
    LRRK2["LRRK2"] -->|"associated"| Parkinson_s_disease["Parkinson's disease"]
    LRRK2["LRRK2"] -->|"regulates"| SNCA["SNCA"]
    LRRK2["LRRK2"] -->|"causes"| Parkinson_s_disease_1["Parkinson's disease"]
    LRRK2["LRRK2"] -.->|"inhibits"| Parkinson["Parkinson"]
    LRRK2["LRRK2"] -->|"implicated in"| Parkinson_2["Parkinson"]
    GABARAP["GABARAP"] -->|"binds"| LRRK2["LRRK2"]
    STING["STING"] -->|"activates"| LRRK2["LRRK2"]
    CASM_pathway["CASM pathway"] -->|"activates"| LRRK2["LRRK2"]
    GABARAP_3["GABARAP"] -->|"regulates"| LRRK2["LRRK2"]
    style LRRK2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1699)

Target	Relation	Type	Str
LRRK2	encodes	protein	0.00
PARKINSON	associated_with	gene	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00
Parkinson	associated_with	disease	1.00
Parkinson	causes	disease	1.00
PARKIN	associated_with	gene	0.98
Parkinson Disease	causes	disease	0.95
Als	associated_with	disease	0.95
Familial Parkinson'S Disease	associated_with	disease	0.95
Parkinson's Disease	associated_with	disease	0.95
Macroautophagy	regulates	process	0.95
Autophagy Process	regulates	process	0.95
Parkinson Disease	risk_factor_for	disease	0.95
Parkinson	therapeutic_target	disease	0.95
RAB	interacts_with	protein	0.95
Parkinson'S Disease	therapeutic_target	disease	0.95
Parkinson's Disease	causes	disease	0.95
Mitochondrial Protection	inhibits	process	0.95
Parkinson'S Disease	causes	disease	0.95
Rab GTPases	phosphorylates	protein	0.92
Autophagy Pathway	involved_in	pathway	0.90
autophosphorylation	upregulates	process	0.90
Chaperone-Mediated Autophagy	modulates	pathway	0.90
Kinase Activation	involved_in	mechanism	0.90
Parkinson's disease	regulates	disease	0.90
α-Synuclein Oligomer Accumulation	associated_with	process	0.90
RAB GTPASES	phosphorylates	protein	0.90
Paneth Cell Dysfunction	causes	phenotype	0.90
PINK1/parkin-mediated mitophagy	inhibits	pathway	0.90
Monocytes	expressed_in	cell_type	0.90
Lysosomal stress	associated_with	process	0.90
RAB8A	phosphorylates	protein	0.90
Crohn's Disease	risk_factor_for	disease	0.90
Autophagy-Lysosomal Pathway	regulates	pathway	0.90
MEK	activates	protein	0.90
Α-SYNUCLEIN	associated_with	protein	0.90
oxidative stress response	participates_in	pathway	0.90
Serine 1292 Autophosphorylation	phosphorylates	biomarker	0.90
G2019S LRRK2	associated_with	protein	0.90
RAB PROTEINS	targets	protein	0.90
RAB10 phosphorylation	regulates	phenotype	0.90
G2019S mutation	associated_with	compound	0.90
Sporadic Parkinson'S Disease	implicated_in	disease	0.90
RAB12 phosphorylation	regulates	phenotype	0.90
MLi-2	targets	drug	0.90
Parkinson's disease	activates	disease	0.90
PARKINSON DISEASE	associated_with	disease	0.90
Type I Interferon Signaling	modulates	pathway	0.90
NRF2	regulates	protein	0.90
NFE2L2	inhibits	gene	0.90

Incoming (926)

Source	Relation	Type	Str
LRRK2	encodes	gene	0.00
entities-histone-modifications	interacts_with	wiki	0.00
entities-snx5	associated_with	wiki	0.00
PARKINSON'S DISEASE	associated_with	gene	1.00
RAB29	reduces endogenous	protein	1.00
RAB29	operates in a common pathway with	protein	1.00
RAB29	recruits	protein	1.00
GABARAP	binds	gene	0.95
BIIB094	targets	drug	0.95
G2019S	associated_with	biomarker	0.95
LRRK2 Inhibitors	inhibits	drug	0.95
LRRK2 kinase inhibitors	inhibits	drug	0.95
STING	activates	protein	0.90
RAB29	regulates	protein	0.90
CASM pathway	activates	pathway	0.90
INTERFERON GAMMA	upregulates	protein	0.90
RAB	activates	protein	0.90
Alternative Polyadenylation	modulates	process	0.90
MLi-2	inhibits	drug	0.90
PF-06447475	inhibits	drug	0.90
PARKINSON'S DISEASE	therapeutic_target	gene	0.90
ALZHEIMER'S DISEASE	associated_with	disease	0.88
PPM1H	inhibits	protein	0.88
CRISPR-Cas9	targets	process	0.85
PRKN	interacts_with	gene	0.85
PINK1	epistasis_with	gene	0.85
RAB29	recruits_to_TGN	gene	0.85
Endolysosomal Dysfunction	activates	process	0.85
PIKFYVE	regulates	protein	0.85
VPS35	associated_with	protein	0.85
Oxidative Stress	activates	process	0.85
MIRO1	interacts_with	protein	0.80
GCASE	interacts_with	protein	0.80
Environmental Toxicants	activates	compound	0.80
Chaperone Network	regulates	pathway	0.80
GABARAP	regulates	protein	0.80
EEF2	phosphorylates	gene	0.80
lysosome damage	activates	phenotype	0.80
IFN	interacts_with	gene	0.80
NEURODEGENERATION	associated_with	gene	0.80
PINK1	associated_with	gene	0.80
Cigarette Smoking	activates	compound	0.75
GLUTAMATERGIC	inhibits	cell_type	0.70
DOPAMINERGIC	inhibits	cell_type	0.70
LAMP1	activates	gene	0.70
ACHE	activates	gene	0.70
ATP13A2	causes	gene	0.70
DYRK1A	activates	gene	0.70
GSK3B	activates	gene	0.70
FOXP3	activates	gene	0.70

Targeting Hypotheses (9)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
G2019S primarily raises baseline LRRK2 kinase activity rathe	0.790	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
Therapeutic Window Exists Because Amplified Signals (Not Bas	0.780	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
RAB29 Is the Critical Molecular Switch That Determines Wheth	0.710	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes	0.680	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation	0.666	neurodegeneration	Does LRRK2's role as a lysosomal volume

LRRK2 Haploinsufficiency Traps Microglia in Senescence-Like	0.650	Parkinson's disease	-
LRRK2 G2019S Uncouples RAB29-Dependent Spatial Control from	0.640	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysos	0.620	neurodegeneration	Test Hypothesis Fixtures
Dual-Mechanism Model: G2019S Increases Both Baseline AND Sig	0.550	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo

Mentioning Analyses (8)

Scientific analyses that reference this entity

LRRK2 Risk Variants: Lysosomal Membrane Dynamics in DA vs Striatal Neurons

neurodegeneration | 2026-04-27 | 0 hypotheses

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

neurodegeneration | 2026-04-24 | 5 hypotheses Top: 0.790

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.666

Neuroinflammation and microglial priming in early Alzheimer's Disease

neurodegeneration | 2026-04-04 | 14 hypotheses Top: 0.651

Immune atlas neuroinflammation analysis in neurodegeneration

Neuroinflammation | 2026-04-03 | 8 hypotheses Top: 0.681

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Continual correlation noted between LRRK2 mutations and pain emergence	genetic_association	Parkinson's disease	0.500	0.00	human	extracted	N/A
LRRK2/GBA Mutation Carrier Resilience — Why Some Carriers Never Develo	validation	Parkinson's Disease	0.400	0.50	human	completed	$2,730,000

Related Papers (12)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Protective or Pathogenic? Kinase activity and the neurodevelopmental origins of [PMID:41344986]	Gatto EM, Espay AJ, Espindola M, Da Prat	Parkinsonism & related disorde	2026
LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopa [PMID:41128923]	Buck SA, Malankhanova T, Strader S, Ma E	Acta neuropathologica	2025
RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome hom [PMID:39343966]	Li X, Zhu H, Huang BT, Li X, Kim H, Tan	Nature communications	2024
Pathological α-synuclein recruits LRRK2 expressing pro-inflammatory monocytes to [PMID:35012605]	Xu E, Boddu R, Abdelmotilib HA, Sokratia	Molecular neurodegeneration	2022
Exploring the focal role of LRRK2 kinase in Parkinson's disease. [PMID:35147886]	["Kumar Sachin", "Behl Tapan", "Sehgal A	Environmental science and poll	2022
Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease. [PMID:35521944]	Wang S, Unnithan S, Bryant N	Mov Disord	2022
R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in [PMID:34125248]	Fan, Nirujogi, Garrido, Ruiz-Martín	Acta neuropathologica	2022
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
Rab GTPases as Physiological Substrates of LRRK2 Kinase. [PMID:31138985]	Seol W, Nam D, Son I	Exp Neurobiol	2019
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018
Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab [PMID:29127255]	["Fan Ying", "Howden Andrew J M", "Sarha	The Biochemical journal	2018

Debates (9)

Multi-agent debates referencing this entity

How do GWAS-identified PD risk variants at the LRRK2 locus alter lysosomal membr

closed · Rounds: 6 · Score: 0.89 · 2026-04-27

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

closed · Rounds: 4 · Score: 0.74 · 2026-04-24

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

closed · Rounds: 4 · Score: 0.85 · 2026-04-16

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 4 · Score: 0.86 · 2026-04-12

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 5 · Score: 0.95 · 2026-04-12

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

closed · Rounds: 4 · Score: 0.85 · 2026-04-03

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

closed · Rounds: 3 · Score: 0.68 · 2026-04-02

Related Research

Hypotheses and analyses mentioning LRRK2 in their description or question text

LRRK2

Understanding Entity Pages

Summary

Wiki Pages (21)

LRRK2 — Leucine Rich Repeat Kinase 2

LRRK2 Kinase Activation and Endolysosomal Dysfunction in Parkinson's Disease

LRRK2 Pathway in Parkinson's Disease

LRRK2 G2019S

LRRK2 Transgenic Mouse Model for Parkinson's Disease

LRRK2 Consortium

Pathway Diagram

Outgoing (1699)

Incoming (926)

Targeting Hypotheses (9)

Mentioning Analyses (8)

LRRK2 Risk Variants: Lysosomal Membrane Dynamics in DA vs Striatal Neurons

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

Neuroinflammation and microglial priming in early Alzheimer's Disease

Immune atlas neuroinflammation analysis in neurodegeneration

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Digital biomarkers and AI-driven early detection of neurodegeneration

Experiments (2)

Related Papers (12)

Debates (9)

How do GWAS-identified PD risk variants at the LRRK2 locus alter lysosomal membr

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

Related Research

LRRK2 G2019S Uncouples RAB29-Dependent Spatial Control from Kinase Activity (H7)

LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysosomal Enhancement

Dual-Mechanism Model: G2019S Increases Both Baseline AND Signal-Dependent Phosph

LRRK2

Understanding Entity Pages

Summary

Wiki Pages (21)

LRRK2 — Leucine Rich Repeat Kinase 2

LRRK2 Kinase Activation and Endolysosomal Dysfunction in Parkinson's Disease

LRRK2 Pathway in Parkinson's Disease

LRRK2 G2019S

LRRK2 Transgenic Mouse Model for Parkinson's Disease

LRRK2 Consortium

Parabacteroides goldsteinii Mitigation of Parkinsonism in LRRK2 Mice

LRRK2-GBA Combination Therapy for Parkinson's Disease

LRRK2 (Leucine-Rich Repeat Kinase 2) — Comprehensive Gene Review

LRRK2 Kinase-Targeting Therapies

LRRK2 Kinase Pathway in Parkinson's Disease

LRRK2→Kinase→Autophagy→PD Causal Chain

LRRK2 Signaling Pathway in Parkinson's Disease

LRRK2 Therapeutics: Investment Landscape Analysis

alpha-synuclein-LRRK2 Crosstalk

LRRK2 Pathway in PD

LRRK2 Signaling Pathway in Parkinson's Disease

AAV-LRRK2 IND-Enabling Study Design

LRRK2/GBA Mutation Carrier Resilience — Why Some Carriers Never Develop PD

LRRK2 Inhibitor Therapy

LRRK2 Kinase Inhibition in Parkinson's Disease - Therapeutic Mechanism

Pathway Diagram

Outgoing (1699)

Incoming (926)

Targeting Hypotheses (9)

Mentioning Analyses (8)

LRRK2 Risk Variants: Lysosomal Membrane Dynamics in DA vs Striatal Neurons

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

Neuroinflammation and microglial priming in early Alzheimer's Disease

Immune atlas neuroinflammation analysis in neurodegeneration

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Digital biomarkers and AI-driven early detection of neurodegeneration

Experiments (2)

Related Papers (12)

Debates (9)

How do GWAS-identified PD risk variants at the LRRK2 locus alter lysosomal membr

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

Related Research

LRRK2 G2019S Uncouples RAB29-Dependent Spatial Control from Kinase Activity (H7)

LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysosomal Enhancement

Dual-Mechanism Model: G2019S Increases Both Baseline AND Signal-Dependent Phosph