pTDP-43 is, therefore, thought to have an essential role in ALS pathogenesis, suggesting its involvement in both loss-of-function (i.e., perturbation of nuclear TDP-43 function) [52] and gain-of-function (i.e., splicing of selected RNA targets; proteasome inhibition) [53] pathological mechanisms. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.