In a significant population of patients (~95 % ALS and ~50 % FTLD), TDP-43 positive intracellular inclusions are present in the CNS even though the TDP-43 gene is not mutated [8-11], raising the question of how wild-type TDP-43 is involved in the pathogenesis of these cases. Here, TARDBP is linked to amyotrophic lateral sclerosis.