TARDBP and amyotrophic lateral sclerosis: Surprisingly, TDP-43 also binds to its pre-mRNA and promotes alternative splicing, resulting in mRNA degradation via nonsense-mediated mRNA decay [136], which provides a feedback loop that controls the homeostasis of FUS and TDP-43 levels, as is disrupted in mutant FUS- and TDP-43 ALS phenotypes [26].