gene

ACSL4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about ACSL4: 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.

742Connections

7Hypotheses

4Analyses

50Outgoing

50Incoming

4Experiments

10Debates

Summary

ACSL4 is a gene implicated in neurodegeneration research. Key relationships include: inhibits, regulates, activates. Associated with ALS, Als, Alzheimer. Connected to 288 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	ACSL4
Full Name	Acyl-CoA Synthetase Long Chain Family Member 4
Chromosome	Xq22.3
Protein Type	Synthetase
Target Class	Enzyme
Function	is an important component in the neurobiology of neurodegenerative diseases.
Mechanism of Action	Enzyme inhibition — blocking ACSL4 prevents incorporation of PUFAs into membrane phospholipids, reducing ferroptosis susceptibility
Primary Expression	various neural cell types:
Druggability	Low (0.41)
Clinical Stage	Phase III
Pathways	Autophagy, Cholesterol, Epigenetic, Ferroptosis, Inflammasome
UniProt ID	[O60488](https://www.uniprot.org/uniprot/O60488)
Ensembl ID	ENSG00000068366
GeneCards	ACSL4
Human Protein Atlas	ACSL4
Associated Diseases	ALS, alzheimer_s_disease, Alzheimer's Disease, CANCER, Carcinoma, Fibrosis
Known Drugs/Compounds	Calycosin, curcumin, CURCUMIN, metformin, METFORMIN, PIOGLITAZONE
Interactions	AKT, ALOX12, ALOX15, ALOX5, ALZHEIMER, ALZHEIMER'S DISEASE
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	ACSL4-Driven Ferroptotic Priming in Disease-Associ ACSL4-Ferroptotic Priming in Stressed Oligodendroc 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferro (+3 more)
KG Connections	740 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    ACSL4["ACSL4"] -->|"activates"| FERROPTOSIS["FERROPTOSIS"]
    ACSL4["ACSL4"] -->|"activates"| LIPID_PEROXIDATION["LIPID_PEROXIDATION"]
    ACSL4["ACSL4"] -->|"associated"| MS["MS"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Als["Als"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Carcinoma["Carcinoma"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Autoimmune["Autoimmune"]
    TMEM16F["TMEM16F"] -->|"regulates"| ACSL4["ACSL4"]
    MIR130B3P["MIR130B3P"] -.->|"inhibits"| ACSL4["ACSL4"]
    SLC7A11["SLC7A11"] -->|"therapeutic target"| ACSL4["ACSL4"]
    MYC["MYC"] -->|"regulates"| ACSL4["ACSL4"]
    style ACSL4 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (536)

Target	Relation	Type	Str
ACSL4	encodes	protein	0.00
FERROPTOSIS	activates	phenotype	1.00
Ferroptosis	mediates	process	0.95
Ferroptosis	associated_with	process	0.90
Fatty acid activation	catalyzes	mechanism	0.90
Fibrosis	associated_with	disease	0.90
oxidative stress response	participates_in	pathway	0.90
FERROPTOSIS	associated_with	process	0.90
GPX4	associated_with	gene	0.90
PHOSPHATIDYLETHANOLAMINE	acylates	lipid	0.90
ARACHIDONIC_ACID	activates	lipid	0.90
Ferroptosis	activates	pathway	0.90
ferroptosis	mediates	process	0.85
Alzheimer's Disease	associated_with	disease	0.82
ferroptosis	participates_in	pathway	0.82
MICROGLIA	upregulated_in	cell_type	0.80
ferroptosis	associated_with	process	0.80
LIPROXSTATIN-1	pathway_target_of	drug	0.80
SLC7A11	associated_with	gene	0.80
Neurodegeneration	activates	disease	0.75
Multiple Sclerosis	associated_with	disease	0.75
Tumor	inhibits	disease	0.75
ROSIGLITAZONE	associated_with	drug	0.75
LIPID_PEROXIDATION	activates	phenotype	0.72
TNF	inhibits	gene	0.70
MICROGLIA	activates	cell_type	0.70
Pyroptosis	inhibits	pathway	0.70
GSDMD	inhibits	gene	0.70
MICROGLIA	regulates	cell_type	0.70
DEMENTIA	interacts_with	disease	0.70
MYC	regulates	gene	0.70
MICROGLIA	protects_against	cell_type	0.70
GPX4	regulates	gene	0.70
DIABETES	inhibits	disease	0.70
Ferroptosis	inhibits	pathway	0.70
GENES	activates	gene	0.70
Apoptosis	activates	pathway	0.70
PYROPTOSIS	inhibits	gene	0.70
GPX4	inhibits	gene	0.70
unfolded protein response	participates_in	pathway	0.70
Ferroptosis susceptibility	modulates	mechanism	0.70
MS	associated_with	disease	0.70
autophagy pathway	participates_in	pathway	0.70
FERROPTOSIS	inhibits	gene	0.70
Glycolysis	activates	pathway	0.70
Als	regulates	disease	0.65
Fibrosis	activates	disease	0.65
Tumor	activates	disease	0.65
Cancer	regulates	disease	0.65
Ferroptosis	biomarker_for	disease	0.65

Incoming (206)

Source	Relation	Type	Str
ACSL4	encodes	gene	0.00
TMEM16F	regulates	gene	1.00
MIR130B	downregulates	gene	0.95
MIR130B	inhibits	gene	0.95
genes-acsl4	describes	wiki	0.95
Calycosin	binds	compound	0.90
h-var-261452bfb4	targets_gene	hypothesis	0.90
h-var-22c38d11cd	targets_gene	hypothesis	0.90
h-var-f96e38ec20	targets_gene	hypothesis	0.90
h-seaad-v4-26ba859b	targets	hypothesis	0.90
Liproxstatin-1	downregulates	drug	0.85
Montelukast	downregulates	drug	0.85
Cadmium	upregulates	compound	0.80
MIR130B3P	inhibits	gene	0.72
PIOGLITAZONE	inhibits	drug	0.70
SLC7A11	regulates	gene	0.70
ATF4	activates	protein	0.70
JNK	associated_with	gene	0.70
LPS	induces	drug	0.70
MTOR	targets	gene	0.65
MTOR SIGNALING	targets	pathway	0.65
CURCUMIN	regulates	drug	0.65
LIPID PEROXIDATION	regulates	phenotype	0.65
LIPID PEROXIDATION	activates	phenotype	0.65
FERROPTOSIS	targets	phenotype	0.65
METFORMIN	activates	drug	0.65
METFORMIN	treats	drug	0.65
GSDMD	inhibits	gene	0.60
SCD1	inhibits	gene	0.60
HMGCR	inhibits	gene	0.60
TNF	inhibits	gene	0.60
MLKL	inhibits	gene	0.60
GPX4	associated_with	gene	0.60
HK2	activates	gene	0.60
ALOX5	activates	gene	0.60
MTOR	inhibits	gene	0.60
PRKAA1	associated_with	gene	0.60
NRF2	therapeutic_target	gene	0.60
GPX4	therapeutic_target	gene	0.60
TFR1	inhibits	gene	0.60
FTH1	inhibits	gene	0.60
GPX4/SLC7A11	therapeutic_target	gene	0.60
ATG7	biomarker_for	gene	0.60
GSH	activates	gene	0.60
MYC	regulates	gene	0.60
FASN	inhibits	gene	0.60
BAX	inhibits	gene	0.60
ALOX15	inhibits	gene	0.60
FERROPTOSIS	regulates	gene	0.60
INFLAMMATION	therapeutic_target	gene	0.60

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.869	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo	0.779	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4 lipid remodeling creates ferroptosis-prone ALS membran	0.710	neurodegeneration	Ferroptosis in ALS motor neuron vulnerab

ACSL4-Mediated Neuroinflammatory Amplification in Disease-As	0.459	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
Closed-loop tFUS targeting of EC-II SST interneurons to prev	0.403	Alzheimer's disease	Circuit-level neural dynamics in neurode

Mentioning Analyses (4)

Scientific analyses that reference this entity

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

neurodegeneration | 2026-04-18 | 4 hypotheses Top: 0.538

What determines the GPX4/ACSL4 balance that switches microglia from protective t

immunology | 2026-04-15 | 0 hypotheses

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

neurodegeneration | 2026-04-03 | 43 hypotheses Top: 0.893

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

neurodegeneration | 2026-04-03 | 19 hypotheses Top: 0.869

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice	validation	Alzheimer's disease	0.900	5xFAD transgenic mice	proposed	N/A
Transcriptomic profiling and differential expression analysis	exploratory	Alzheimer's disease	0.900	1-month-old APP/PS1 mice cereb	proposed	N/A
SIRPα modulation in mouse models of Alzheimer's disease	validation	Alzheimer's disease	0.900	mouse models of Alzheimer's di	proposed	N/A
Microglial SIRPα expression in human Alzheimer's disease tissue	exploratory	Alzheimer's disease	0.800	human brain tissue	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655]	Jorstad NL, Close J, Johansen N, Yanny A	Science	2023	186
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445]	Qin J, Ma S, Wang J, Huang S, Luan J, He	Cell death & disease	2026	0
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795]	Gao C, Liu B, Zhang R, Tian J, Xin H	Toxicology mechanisms and meth	2026	0
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890]	Rao W, Huang Y, Li J, Chen Q, Sun J et a	J Stroke Cerebrovasc Dis	2026	0
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892]	Lin D, Li K, Kuang W, Chen Z, Zhang M	World J Mens Health	2026	0
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496]	Che L, Zhu L, Zhou L, Zhou Y	Biochim Biophys Acta Rev Cance	2026	0
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570]	Chien Y, Xia R, Zhou D, Ai Y, Wu L et al	Hepatol Commun	2026	0
Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease lin [PMID:41498558]	Singh P, Rath SL	Journal of Alzheimer's disease	2026	0
Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Media [PMID:41873334]	Song C, Wu X, Chen C, Shen B, He Y, Liu	Drug design, development and t	2026	0
Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent [PMID:41662914]	["Xin R", "Zhang J", "Zhang Y", "Dai M",	Free radical biology & medicin	2026	0
Acteoside alleviates sepsis-induced acute lung injury by activating the Nrf2 pat [PMID:41895086]	Wang Y, Zhang W, Zhang M, Zhu Y, Wang W,	Tissue & cell	2026	0
Ferroptosis and microglial polarization in retinal vein occlusion: pathological [PMID:41924362]	Xu J, Sun M, Wang C, Ju P, Guan XD, Xie	International journal of ophth	2026	0
Melatonin Alleviates Erastin-Induced Cell Death by Inhibiting Ferroptosis and Am [PMID:40442550]	Wongjaikam S, Siengdee P, Somnus A, Govi	Neurotoxicity research	2025	0
Acyl-CoA synthetase long-chain family member 4-A novel prognostic marker in cuta [PMID:41918944]	Paria S, Lapides R, Saravi B, Rajagopal	Frontiers in medicine	2025	0
Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in alzhei [PMID:40640358]	Zhu L, Zhou T, Wu L, Zhu X, Chen L, Zhan	Scientific reports	2025	0
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathol [PMID:39510074]	["Zha Xu", "Liu Xicheng", "Wei Mengping"	Cell metabolism	2025	0
Upregulation of MAM by C99 disrupts ACSL4 activity and phospholipid homeostasis [PMID:41394684]	Montesinos J, Yun TD, Salomón-Cruz ID, A	bioRxiv : the preprint server	2025	0
Danggui Shaoyao San ameliorates Alzheimer's disease by regulating lipid metaboli [PMID:40271063]	Gong K, Zhou S, Xiao L, Xu M, Zhou Y, Lu	Frontiers in pharmacology	2025	0
Single-cell spatial transcriptomics reveals distinct patterns of dysregulation i [PMID:39103533]	Johnston KG, Berackey BT, Tran KM, Gelbe	Molecular psychiatry	2025	0
Deferiprone in Alzheimer Disease: A Randomized Clinical Trial. [PMID:39495531]	Ayton S, Barton D, Brew B, Brodtmann A,	JAMA neurology	2025	0

Debates (10)

Multi-agent debates referencing this entity

Debate: LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Primin

closed · Rounds: 4 · Score: 0.12 · 2026-04-27

Debate: ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE P

closed · Rounds: 4 · Score: 0.42 · 2026-04-27

Debate: LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability i

closed · Rounds: 4 · Score: 0.48 · 2026-04-27

Debate: ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes

closed · Rounds: 4 · Score: 0.47 · 2026-04-27

Should '40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Sele

closed · Rounds: 4 · Score: 0.52 · 2026-04-27

Should 'ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matt

closed · Rounds: 4 · Score: 0.72 · 2026-04-27

The debate highlighted compelling correlative evidence for ferroptosis markers i

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

While ACSL4-driven ferroptosis was strongly supported, the molecular triggers th

closed · Rounds: 4 · Score: 0.80 · 2026-04-16

What gene expression changes in the aging mouse brain predict neurodegenerative

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

What cell types are most vulnerable in Alzheimers Disease based on SEA-AD transc

closed · Rounds: 4 · Score: 0.90 · 2026-04-03

Related Research

Hypotheses and analyses mentioning ACSL4 in their description or question text

ACSL4-Mediated Neuroinflammatory Amplification in Disease-Associated Microglia

Score: 0.459 · Alzheimer's Disease · 2026-04-26

ACSL4 (acyl-CoA synthetase long-chain family member 4) drives neuroinflammatory amplification in disease-associated micr

Closed-loop tFUS targeting of EC-II SST interneurons to prevent ACSL4-mediated f

Score: 0.403 · Alzheimer's disease · 2026-04-26

Somatostatin-positive interneurons in entorhinal cortex layer II serve dual roles as gamma frequency gatekeepers and mic