Resolve: TDP-43 condensation thermodynamics as a therapeutic target and biomarker for nuclear-cytoplasmic compartmentalization

Falsifiable prediction from high-scoring hypothesis (score=0.724, gene=TARDBP). Hypothesis: Does TDP-43 liquid-liquid phase separation (LLPS) state — measured by FRAP — predict therapeutic response to nuclear import receptor (IPO4/IPO9) treatment in ALS/FTD neurons? Success criteria: 1. FRAP recovery half-time of TDP-43-eGFP is >3× slower in ALS/FTD patient iPSC neurons vs controls. 2. IPO4/IPO9 treatment (10μM, 72h) increases nuclear TDP-43 by >40% (nuclear/cytoplasmic ratio by IF). 3. IPO4 treatment restores FRAP recovery to within 20% of control values in ALS neurons. 4. Nuclear pore integrity marker (mAb414) increases by >30% after IPO4 treatment, validated by EM.