Since the cytoplasmic mislocalization of TDP-43 can lead to a gain-of-function in the cytoplasm and depletes its nuclear level to cause a loss-of-function in the nucleus, understanding how mutant TDP-43 accumulates in the cytoplasm is important for elucidating the pathogenesis of ALS, FTLD, and other neurological disorders. Here, TARDBP is linked to amyotrophic lateral sclerosis.