After the identification of TDP-43 as the major protein component of intraneuronal aggregates in ALS and FTLD, several pathological mutations in the TARDBP gene have been identified in subjects affected by familial and sporadic forms of ALS and in a restricted number of subjects with FTLD [240,247,248,249], thus confirming a direct link between this protein and pathology. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.