TARDBP and amyotrophic lateral sclerosis: In keeping with these fundamental functions, cytoplasmic TDP-43 mislocalisation and aggregation in ALS-affected neurons are supposed to trigger neurodegeneration not only by the acquisition of a potentially toxic activity in the cytoplasm (“gain-of-function” hypothesis) but also by the loss of the protein’s physiological functions (“loss-of-function” hypothesis) [51,52,53,54].