It is well established that neuronal TDP-43 cytoplasmic inclusions are present in several different neurodegenerative diseases, such as FTD, ALS and Alzheimer and that the sequestration of this protein in aggregates may create gain- and loss-of-function events causing (directly or indirectly) cellular toxicity or alteration of the TDP-43-regulated gene expression. Here, TARDBP is linked to amyotrophic lateral sclerosis.