{"artifact":{"id":"hypothesis-hyp-lyso-snca-1d58cf205e1f","artifact_type":"hypothesis","entity_ids":"[]","title":"LAMP2A Liquid-Liquid Phase Separation Defects in Dopaminergic Neurons Create Selective Vulnerability to SNCA-Mediated CMA Blockade","quality_score":0.7833,"created_by":"hypothesis_page_handler","provenance_chain":"[]","content_hash":"c3c4e5404ec31c6c296b396afa0cbc39aea2cddb0b34cd26a81d180d7c349a0e","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-28T11:41:20.404956"},"description":"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","hypothesis_id":"hyp-lyso-snca-1d58cf205e1f","_schema_version":1},"created_at":"2026-04-28T04:41:20.405057-07:00","updated_at":"2026-04-28T04:41:20.405057-07:00","version_number":3,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":null,"citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"2a454f34-7ad5-4df9-b57d-e099912eb5f4","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"hypothesis_page_handler"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[{"source_artifact_id":"bench_pd_dopaminergic_expression_signature_v1","link_type":"related","strength":0.75,"evidence":"PD Dopaminergic Neuron Expression Signature benchmark seeded to evaluate hypotheses/gaps related to hypothesis-hyp-lyso-snca-1d58cf205e1f (forge:benchmark_seed_2026-04-28)."}],"current_artifact_id":"hypothesis-hyp-lyso-snca-1d58cf205e1f","is_canonical":true,"supersede_chain":["hypothesis-hyp-lyso-snca-1d58cf205e1f"]}