TDP-43 proteinopathy (mislocalized, misfolded TDP-43 protein; Fig. 1A, B) was first recognized as a pathological feature in diseases along what is now considered to be a pathological spectrum that includes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) (20, 21). The gene discussed is TARDBP; the disease is frontotemporal dementia.