TARDBP and amyotrophic lateral sclerosis: TDP-43 pathology in motor neurons of the spinal cord is the pathological hallmark of ALS (Aizawa et al, 2010; Arai et al, 2006; Neumann et al, 2006), and mislocalization of TDP-43 is induced by exaggerated calpain-mediated cleavage of TDP-43 into aggregation-prone fragments, although further activation of calpain cleaves the aggregation-prone fragments into smaller soluble fragments (Yamashita et al, 2012a).