Despite the recognized importance of TDP-43 in ALS, it is still unclear whether the pathogenesis of ALS is related to its reduced physiological function, since wild-type TDP-43 is sequestered in inclusion bodies and unable to interact with its physiological targets, or if it is due to the formation of toxic aggregates containing TDP-43 (Scotter et al., 2015). Here, TARDBP is linked to amyotrophic lateral sclerosis.