Mice that are deficient in CatS have a reduced susceptibility to models that recapitulate autoimmune disorders such as the collagen-induced arthritis (CIA)model for rheumatoid arthritis [16], whilst pharmacological inhibition of CatS using orally-active therapeutic doses of brain-penetrant drugs serves to effectively reduce clinical scores in both the CIA model [17] and the encephalomyelitis (EAE) model of multiple sclerosis [18]. Here, PIMREG is linked to encephalomyelitis.