Among the most studied immune checkpoints are cytotoxic T-lymphocyte antigen 4 (CTLA-4); programmed death-1 (PD-1) and its ligand, PD-L1; and inducible T-cell costimulator (ICOS), all of which are under active investigation in the context of autoimmune disorders, including RA (Figure 1). The gene discussed is ICOS; the disease is Autoimmunity.