Human IL-1R was initially cloned from T cells and fibroblasts. It belongs to the family of IL-1 like receptors that, in conjuction with Toll-like receptors, constitute a phylogenetically conserved family of proteins. A characteristic of this family is the presence of a TIR domain (Toll/IL-1R domain) in the cytoplasmic portion. IL-1R contains a large cytoplasmic region, and the extracellular region consists of three immunoglobulin-like domains. After IL-1 binds to IL-1R1, IL-1R accessory protein (AcP) is recruited to form a high affinity IL-1R1-IL-1RAcP heterodimeric receptor. Subsequently, the IL-1RI-IL-1RAcP complex recruits the myeloid differentiation protein (MyD88), IRAKs, and TNF receptor associated factor 6 (TRAF6). The downstream signaling cascade involves activation of NFκB, mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways. Soluble IL-1RI and IL-1RII bind to IL-1β with higher affinity than do IL-1α and IL-1Ra, preventing IL-1RI signaling. IL-1 is induced and activated after tissue injury, and IL-1/IL-1R play an essential role in inflammatory conditions such as sepsis, rheumatoid arthritis, inflammatory bowel disease, keratinocyte transformation, and carcinogenesis.