TDP-43 proteinopathy, characterized by the accumulation of the hyper-phosphorylated, fragmented, and aggregated TDP-43 in the cytoplasm and depletion of TDP-43 from the nucleus, is a pathologic hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS)4,5, frontotemporal lobar degeneration (FTLD)5–7, Alzheimer’s disease (AD)8–10, Huntington’s diseases (HD)11, and limbic-predominant age-related TDP-43 encephalopathy (LATE)12,13. Here, TARDBP is linked to juvenile Huntington disease.