G3BP1 orchestrates stress granule assembly and may serve as the nucleation hub that seeds pathological TDP-43 and FUS aggregates in ALS. If G3BP1 is genuinely rate-limiting (not merely co-localizing), then partial G3BP1 depletion should dissolve the seeding threshold without abolishing normal stress responses. The critical distinction is between G3BP1 as a structural scaffold vs. an active catalytic nucleator — with different intervention implications. Falsifiable prediction: 60% G3BP1 knockdown via siRNA in ALS-iPSC motor neurons should reduce TDP-43 nuclear clearance by ≥60% and FUS cytoplasmic mislocalization by ≥50% under arsenite-induced stress (100 μM, 30 min), while preserving ≥70% normal SG assembly kinetics (TIAR+ SG count). Nucleation rate (ThT half-time in lysate seeding assay) should increase ≥3× with G3BP1 overexpression.