The cathepsin S inhibitor RO5459072 is the clinical lead molecule at F. Hoffman-La Roche, designed for treatment of autoimmune diseases associated with MHCII peptide loading and is a selective, potent, and competitive oral inhibitor of the active site of cathepsin S. RO5459072 has been shown to reduce CD4 T cell and dendritic cell activation as well as autoantibody production in a preclinical model of spontaneous systemic lupus erythematosus and lupus nephritis (16). Here, CTSS is linked to autoimmune disease.