IL1RAP

IL1RAP, short for interleukin-1 receptor accessory protein, is a membrane-bound protein that serves as a coreceptor in signaling by the interleukin-1 (IL-1) receptor family. It is essential for transducing signals initiated by IL-1α and IL-1β through their receptor IL-1R1 and also participates in signaling for related cytokines such as IL-33 via the ST2 receptor (IL1RL1) axis. By forming a receptor complex with IL-1R1 or ST2, IL1RAP enables downstream signaling events that regulate inflammatory responses in numerous cell types.

Structurally, IL1RAP is a type I transmembrane protein with an extracellular region containing immunoglobulin-like domains, a single transmembrane segment, and a cytoplasmic tail. The extracellular portion participates in receptor assembly, while the cytoplasmic region helps recruit adaptor proteins that initiate intracellular signaling cascades. The canonical pathway activated through this complex involves MyD88, IRAK kinases, and TRAF6, leading to the activation of NF-κB and MAP kinase pathways and the transcription of pro-inflammatory genes.

Expression of IL1RAP is widespread, with detection in various immune cells such as monocytes, neutrophils, dendritic cells, and endothelial cells, as well as in some non-immune tissues. Its expression can be modulated by inflammatory stimuli, reflecting its role in amplifying or shaping inflammatory responses. In addition to its membrane-bound form, soluble forms of IL1RAP have been described in some contexts and may influence signaling dynamics.

Clinically, IL1RAP has been studied for associations with inflammatory and autoimmune diseases, given its central role in IL-1 family signaling. Because of its pivotal function in mediating pro-inflammatory signals, IL1RAP remains a point of interest for therapeutic strategies aiming to modulate inflammatory pathways.