Although the occurrence of ALS-causing TDP-43 mutations is rare in the patient population, the close correlation between the pathology observed in these mice and that seen in the majority of TDP-ALS patients suggests that these animals provide a viable model for studying the impact and progression of TDP-43 pathology in the central nervous system, and help to elucidate mechanisms that may underlie disease progression. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.