Specific lipid perturbations (bis(monoacylglycero)phosphate enrichment, cardiolipin externalization) create membrane microenvironments that expose distinct amyloid-competent conformers, allowing one misfolded protein to template another's beta-sheet formation with lipid-mediated specificity.
Curated pathway from expert analysis
flowchart TD
A["Lysosomal Membrane Stress<br/>PLD3 Dysfunction or Mutation"]
B["BMP Bis-Monoacylglycerophosphate Enrichment<br/>Late Endosome Lipid Signature"]
C["Cardiolipin Externalization<br/>Mitochondrial Lipid Exposed"]
D["Membrane Microenvironment Switch<br/>Unique Lipid Topology Created"]
E["Amyloid-Competent Conformer Exposure<br/>Protein Misfolding Nucleation Sites"]
F["Cross-Seeding Recognition Events<br/>Specificity Switched by Lipid Context"]
G["Multi-Protein Aggregate Propagation<br/>Tau-SNCA-TDP43 Co-Seeding"]
A --> B
A --> C
B --> D
C --> D
D --> E
E --> F
F --> G
style D fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for PLD3 yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for PLD3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.