TARDBP and amyotrophic lateral sclerosis: TDP-43, therefore plays a clear and essential role as a nuclear protein; pathologically, TDP-43 has a less understood role, as hypothesized to be translocated to the cytoplasm [57,58,59,60,61] due to calpain-initiated cleavage at the proposed ‘prion-prone’ C-terminal [62], especially in TARDBP-associated ALS.