TARDBP and amyotrophic lateral sclerosis: TDP-43 pathology is the most reliable hallmark of motor neuron pathology of ALS, in which TDP-43 is abnormally insoluble, mislocalized, hyperphosphorylated, and fragmented in motor neurons (Arai et al., 2006; Neumann et al., 2006; Kwong et al., 2007; Chen-Plotkin et al., 2010).