IL36G encodes interleukin-36 gamma, a pro-inflammatory cytokine that plays critical roles in skin inflammation and immune responses. IL36G functions primarily through keratinocyte activation, where it induces expression of multiple chemokines including CCL3, CCL4, CCL5, CXCL8, and CCL20, as well as pro-inflammatory mediators like TNF and S100A7 1. The protein signals through the IL1RL2/IL-36R receptor, activating NF-κB and MAPK pathways 2. In psoriasis pathogenesis, IL36G expression is highest in granular layer keratinocytes and shows an inverse relationship with PCSK9 expression 3. Single-cell studies reveal that semimature dendritic cells express IL36G in psoriatic lesions, contributing to inflammatory amplification 4. IL36G also participates in neutrophil extracellular trap (NET)-mediated inflammation through TLR4/IL-36R crosstalk, promoting psoriasis-like skin inflammation 2. Beyond skin, IL36G-producing neutrophil-like monocytes contribute to cancer cachexia by promoting skeletal muscle wasting 5. The cytokine is upregulated in response to mycobacterial antigens, suggesting involvement in antimicrobial immune responses 6. Clinically, IL36G represents a potential therapeutic target for inflammatory skin diseases and cancer-associated cachexia.