IL18RAP

IL18RAP (Interleukin 18 Receptor Accessory Protein), also known as IL-1RAPL2 or IL-1R7, functions as an essential accessory subunit of the IL-18 receptor complex. It forms a heterodimeric receptor with IL-18Rα to enable high-affinity binding of IL-18, a pro-inflammatory cytokine structurally related to the IL-1 family. Upon ligand engagement, IL18RAP recruits downstream adaptor proteins such as MyD88, initiating signaling cascades that activate NF-κB and MAPK pathways. These pathways drive inflammatory responses by regulating cytokine production, immune cell activation, and apoptosis. The IL-18/IL18RAP axis is implicated in Th1-mediated immunity and inflammasome-associated diseases, positioning it as a key modulator of both innate and adaptive immune responses.
Dysregulation of IL18RAP is linked to autoimmune disorders (e.g., rheumatoid arthritis, Crohn’s disease), allergic inflammation, and certain cancers. Elevated IL-18 signaling through IL18RAP exacerbates tissue damage in chronic inflammation, while genetic polymorphisms correlate with disease susceptibility. Therapeutic strategies targeting this axis include monoclonal antibodies against IL-18 (e.g., tadekinig alfa) and IL-18BP (IL-18 binding protein) fusion proteins, several of which are in Phase II trials for autoinflammatory syndromes. Small-molecule inhibitors disrupting IL18RAP-mediated signaling are under preclinical investigation, with potential applications in cytokine storm management and combination immunotherapy regimens.