Biochemical characterization of the insoluble fractions of ALS patient CNS tissue showed that TDP-43 is aberrantly cleaved into 35 kDa and 25 kDa C-terminal fragments (Neumann et al., 2006) which are aggregation-prone and toxic in cell overexpression models (Igaz et al., 2009; Zhang et al., 2009; Yang et al., 2010; Nonaka et al., 2013). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.