25-kDa C-terminal fragments of TDP-43 (TDP-43208–414) are commonly detected in ALS and FTD-U pathologic specimens, especially in the cerebral cortex, and generation of these fragments is sufficient to initiate a number of events that mirror TDP-43 proteinopathies2,3,20. Here, TARDBP is linked to amyotrophic lateral sclerosis.