IL36RN

IL36RN encodes interleukin-36 receptor antagonist (IL-36Ra), also known as IL-1 family member 5 (IL1F5). This protein acts as a natural antagonist by competitively binding to the IL-36 receptor (IL-36R), thereby inhibiting downstream signaling mediated by IL-36α, β, and γ agonists. It modulates inflammation through the NF-κB and MAPK pathways, regulating keratinocyte activation and immune cell recruitment. Dysregulated IL-36 signaling is implicated in neutrophilic dermatoses, particularly generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP). Autosomal-recessive IL36RN mutations are strongly associated with GPP pathogenesis. Therapeutic agents targeting IL-36R, such as spesolimab (anti-IL-36R monoclonal antibody), have shown efficacy in Phase III trials for GPP. Imsidolimab, another IL-36R antagonist, is under investigation for pustular psoriasis and hidradenitis suppurativa.