IL36A (interleukin 36 alpha) is a pro-inflammatory cytokine that signals through the IL-36 receptor to activate NF-κB and MAPK pathways, driving immune responses at epithelial barriers 1. The primary function of IL36A involves orchestrating skin inflammation by acting on keratinocytes, dendritic cells, and T cells. In keratinocytes, IL36A induces expression of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL1) and pro-inflammatory cytokines (TNF, IL-6, IL-8), while in dendritic cells it promotes maturation and T-cell proliferation 1. Transcriptionally, C/EBPβ acts as a key regulator of IL36A expression in macrophages following LPS stimulation 2. Clinically, IL36A dysregulation is implicated in multiple inflammatory skin diseases including psoriasis, atopic dermatitis, and hidradenitis suppurativa 1. In atopic dermatitis specifically, elevated IL36A expression correlates with stronger clinical response to dupilumab therapy and represents part of a stable disease signature characterized by IL-1 signaling dysregulation 3. Emerging evidence suggests IL36A involvement extends beyond dermatology; increased cerebrospinal fluid IL36A levels associate with bipolar disorder risk 45. The IL-36/IL-36R axis has been recognized as a promising therapeutic target for inflammatory disorders.