Available information is consistent with the view that TIR8/SIGIRR is a conserved and broadly expressed negative regulator of inflammation, tissue damage, autoimmunity, and cancer (Figure 3; Table 2), acting by negatively regulating ILRs- or TLRs-dependent signaling, possibly by interfering with the recruitment of TIR domain containing signaling molecules (Figure 2). The gene discussed is IARS1; the disease is cancer.