TARDBP and amyotrophic lateral sclerosis: In that direction, alteration in the function of TDP-43 is considered one of the main causes of ALS and it has been shown that pathological variations in the intracellular levels of this protein (both gain or loss of function) were able to cause neurodegeneration, indicating that tight control of TDP-43 expression is crucial to prevent neurological phenotypes [40–42].