Interleukin‐1 receptor accessory protein (IL‐1RAcP) is a member of the immunoglobulin superfamily proteins consisting of soluble and membranous isoforms. IL‐1RAcP plays an essential role in the signaling of the IL‐1 family cytokines such as IL‐1, IL‐33 and IL‐36, as well as tyrosine kinases FLT3 and C‐Kit. IL‐1RAcP generally initiates inflammatory signaling pathway through the recruitment of signaling mediators, including MYD88 and IRAK. Chronic inflammation following prolonged signaling of cytokine receptors is a critical process in the pathogenesis of many inflammatory disorders, including autoimmunity, obesity, psoriasis, type 1 diabetes, endometriosis, preeclampsia and Alzheimer's disease. Recently IL‐1RAcP aberrant signaling has been considered to play a central role in the pathogenesis of these chronic inflammatory diseases. Targeting IL‐1RAcP signaling pathway that was recently considered in clinical trials related to malignancies also indicates its potential as therapeutic target for the inflammatory and autoimmune diseases. This review summarizes the molecular structure, components associated with IL‐1RAcP signaling pathways, and their involvement in the pathogenesis of different inflammatory diseases. We will also discuss the effect of IL‐1RAcP inhibition for treatment proposes.

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