TARDBP and amyotrophic lateral sclerosis: While some of the proposed mechanisms for the generation of the lower molecular weight TDP-43 species in ALS/FTLD include proteolytic cleavage by caspase-3, calpain, or asparaginyl endopeptidases (Zhang et al., 2007; Dormann et al., 2009; Herskowitz et al., 2012; Yamashita et al., 2012), we and others have shown that such moieties can arise from alternative splicing of the TARDBP gene (Wang et al., 2002, 2004; Ayala et al., 2011; Polymenidou et al., 2011; Avendaño-Vázquez et al., 2012; D'Alton et al., 2015; Xiao et al., 2015).