These proteases have been linked previously to the generation of toxic fragments of many disease-causing proteins, including the polyQ proteins ataxin-3 in Machado–Joseph disease (MJD) and huntingtin in HD, as well as α-synuclein in Parkinson disease (PD), TDP-43 in amyotrophic lateral sclerosis (ALS) or tau in AD [21–26]. This evidence concerns the gene ATXN3 and amyotrophic lateral sclerosis.