A gain-of-toxicity mechanism for early pathogenesis of FTLD-TDP or ALS-TDP has been suggested in view of the aberrant RNA metabolism and/or purturbed autoregulation of TDP-43 caused by mutant TDP-43 in different mouse models [5, 24, 58, 59, 86, 89]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.