This challenge targets the hypothesis: **PINK1/Parkin–TREM2 Axis: Convergent Mitophagy Failure Unifies PD (SNCA/αSyn) and AD (tau/Abeta) Pathology** **Hypothesis Summary:** Convergence hypothesis: PINK1/Parkin-mediated mitophagy dysfunction in neurons and TREM2-mediated microglial mitophagy failure represent a unified convergence point driving both Parkinson's disease (PD) and Alzheimer's disease (AD) pathophysiology. PD-specific mechanism: PINK1 kinase phosphorylates Parkin (PRKN) and ubiquitin at mitochondrial outer membrane, triggering clearance of damaged mitochondria. In PD, mutations in PINK1 (PARK6) or PRKN (PARK2) impair this clearance, leading to mitochon **Falsifiable Predictions:** 1. Pharmacological modulation of PINK1 will alter neurodegeneration markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $128,000 USD (composite score 0.780) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.