Single-immunoglobulin IL-1 receptor-related (SIGIRR) protein, also known as TIR-8, is a member of the TLR/IL-1R family that has been extensively characterised as an inhibitor of IL-1R and TLR signalling, probably through direct interaction with these receptors, MyD88, IRAK1 or TRAF6 [67] (Figure 1).