Given that abnormal processing and mislocalization of the 43-kDa TAR DNA-binding protein (TDP-43) occurs in a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) [1], [2], much effort has been made to understand the molecular bases of the abnormalities that occur in TDP-43 proteinopathies. The gene discussed is TARDBP; the disease is frontotemporal dementia.