Ninety-seven percent of patients with ALS and 50% of patients with FTD have cytoplasmic TDP-43 aggregates within neurons,332 and mutations in TARDBP, the gene encoding TDP-43, have been identified in patients with ALS or FTD,306,333 indicating a mechanistic link between TDP-43 and ALS/FTD and also suggesting a common underlying mechanism, which prompts the use of TDP-43 mutant transgenic mice to study TDP-43-related neurodegeneration in ALS and FTD. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.