The first aggregated protein to be identified was Cu/Zn superoxide dismutase (SOD1; Rosen et al., 1993), then trans-active DNA binding protein-43 (TDP-43; Arai et al., 2006; Neumann et al., 2006), along with fused in sarcoma/translocated in liposarcoma (FUS; Kwiatkowski et al., 2009; Vance et al., 2009), see Blokhuis et al. (2013) for a more extensive review on toxic protein accumulation in ALS. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.