IL1RAcP

IL1 receptor accessory protein (IL1RAP) is a type I transmembrane glycoprotein that belongs to the interleukin-1 receptor (IL-1R) superfamily. It functions as a co-receptor essential for signal transduction by IL-1 family cytokines, most notably IL-1 alpha and IL-1 beta. In typical signaling, IL-1RAP associates with the IL-1 receptor type I (IL1R1) after ligand binding, enabling recruitment of downstream adaptor proteins such as MyD88 and the activation of NF-κB and MAPK pathways, which drive inflammatory gene expression.

In addition to IL-1 signaling, IL1RAP participates in signaling for other IL-1 family members. It serves as a shared component in signaling by proteins such as IL-33 through its receptor ST2 (IL1RL1) and by certain IL-36 cytokines in combination with IL36R, underscoring its role as a common co-receptor within this cytokine family.

Structure and expression: The extracellular domain of IL1RAP contains immunoglobulin-like repeats, facilitating ligand-receptor interactions, while the cytoplasmic tail is short and does not initiate signaling by itself. The protein exists in membrane-bound forms and, in some contexts, soluble isoforms may be generated by alternative splicing or proteolytic processing, potentially modulating IL-1–family signaling.

Clinical significance: IL1RAP is essential for IL-1–mediated inflammatory responses and is a focus of research in inflammatory diseases. It is also of interest as a biomarker and therapeutic target in certain cancers, such as acute myeloid leukemia, where IL1RAP is overexpressed on leukemic cells and being explored as a target for immunotherapies.