ST2 is a member of a superfamily containing the interleukin-1 receptor and the Toll-like receptors (TLRs). The TLRs are signaling molecules that recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses. ST2 was originally identified as a protein whose production was stimulated by various proliferation-inducing agents such as PDGF and FGF. More recently, it has been shown to negatively regulate IL-1 receptor and Toll-like receptor (TLR) 4 signaling and to maintain endotoxin tolerance. It has been suggested that the inhibition of TLR4 signaling occurs through the association and sequestering of TLR adaptor molecules such as MyD88 and TIRAP.