This challenge targets the hypothesis: **Lysosomal Cathepsin-Dependent Tau Clearance** **Hypothesis Summary:** ## Mechanistic Overview Lysosomal Cathepsin-Dependent Tau Clearance starts from the claim that modulating not yet specified within the disease context of neurodegeneration can redirect a disease-relevant process. The original description reads: "## Mechanistic Overview Lysosomal Cathepsin-Dependent Tau Clearance starts from the claim that modulating not yet specified within the disease context of neurodegeneration can redirect a disease-relevant process. The original description reads: "# Lysoso **Falsifiable Predictions:** 1. Pharmacological modulation of target pathway 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:** $126,700 USD (composite score 0.767) **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.