TARDBP and amyotrophic lateral sclerosis: In support of this, multiple components of the ubiquitin–proteasome system (UPS) and autophagy pathway were reported to be sequestered within TDP-43 inclusions in ALS/FTD autopsies and disease models [386–390], which has been shown to impair the functionality of these protein quality control systems [390] – potentially initiating a vicious cycle that exacerbates TDP-43 pathology.