This challenge targets the hypothesis: **Biphasic Ketogenic Intervention Protocol** **Hypothesis Summary:** ## Mechanistic Overview Biphasic Ketogenic Intervention Protocol starts from the claim that modulating HMGCS2 within the disease context of metabolic neuroscience can redirect a disease-relevant process. The original description reads: "**Molecular Mechanism and Rationale** The biphasic ketogenic intervention protocol leverages the multifaceted molecular mechanisms of ketone bodies, particularly β-hydroxybutyrate, which functions far beyond simple metabolic fuel provision. The target gene HMGCS2 **Falsifiable Predictions:** 1. Pharmacological modulation of HMGCS2 will alter metabolic neuroscience 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:** $127,325 USD (composite score 0.773) **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.