TARDBP and amyotrophic lateral sclerosis: Nevertheless, a hyper-phosphorylated, ubiquitinated, and cleaved form of TDP-43 (pathological TDP-43) is the major disease protein in ubiquitin-positive, tau-, and α-synuclein-negative FTLD and in ALS (Mackenzie et al., 2011; Brauer et al., 2018).