This challenge targets the hypothesis: **RBM45 Liquid-Liquid Phase Separation Dominance Hijacks RNA Processing Condensates Toward Pathological Aggregation in ALS** **Hypothesis Summary:** RBM45 (RNA Binding Motif Protein 45) is a predominantly neuronal RNA-binding protein that undergoes ALS-associated disease modifications (phosphorylation, oxidative modification) that alter its liquid-liquid phase separation (LLPS) behavior. This hypothesis proposes that in ALS motor neurons, modified RBM45 forms aberrant, stable condensates that dominate RNA processing droplets (nuclear speckles, stress granules), displacing essential granule components (SFPQ, TDP-43, hnRNP A1) into a pathologi **Falsifiable Predictions:** 1. Pharmacological modulation of the RBM45 pathway will alter neurodegeneration markers in validated ALS models by ≥20% relative to controls 2. Genetic knockdown of the key molecular target will reproduce the proposed pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature with sensitivity ≥70% and specificity ≥70% vs healthy controls 4. Therapeutic intervention at the proposed mechanistic node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $135,800 USD (hypothesis-grade, composite score 0.858) **Challenge Type:** Open — any team may submit experimental evidence **Success Criteria:** Peer-reviewed publication or preprint with independent replication demonstrating mechanistic validation of ≥2 of the 4 predictions above.