An important point to consider is that as TARDBP mutations are rare (around 4% of familial cases and up to 1% of sporadic ALS) (Renton et al. 2014), in the great majority of patients, TDP-43 pathology is defined by the exclusion from the nucleus and the cytoplasmic and/or nuclear aggregation of WT TDP-43. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.