This challenge targets the hypothesis: **LAMP2A Liquid-Liquid Phase Separation Defects in Dopaminergic Neurons Create Selective Vulnerability to SNCA-Mediated CMA Blockade** **Hypothesis Summary:** LAMP2A exists in the lysosomal membrane as both monomers and higher-order oligomers that undergo liquid-liquid phase separation (LLPS) to form membrane microdomains essential for SNCA recognition and translocation into the lysosomal lumen. Recent biophysical studies demonstrate that LAMP2A's cytosolic tail contains an intrinsically disordered region capable of mediating homotypic LLPS, creating lipid-raft-like microdomains enriched in chaperone-HSC70. In A9 dopaminergic neurons (vulnerable), LAM **Falsifiable Predictions:** 1. Pharmacological modulation of the LAMP2 pathway will alter neurodegeneration markers in validated neurodegeneration models by ≥20% relative to controls 2. Genetic knockdown of the key molecular target will reproduce the proposed pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature with sensitivity ≥70% and specificity ≥70% vs healthy controls 4. Therapeutic intervention at the proposed mechanistic node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $128,330 USD (hypothesis-grade, composite score 0.783) **Challenge Type:** Open — any team may submit experimental evidence **Success Criteria:** Peer-reviewed publication or preprint with independent replication demonstrating mechanistic validation of ≥2 of the 4 predictions above.