IL1F10 encodes IL-38, an anti-inflammatory cytokine of the IL-1 family that serves as a critical regulator of immune homeostasis and tissue maintenance. IL-38 is constitutively expressed in epithelial tissues, particularly in differentiated epidermal keratinocytes where its expression is regulated by epigenetic modifications and transcription factors KLF4 and TAp63β 1. The protein functions as an immunomodulatory cytokine that reduces pro-inflammatory responses, including decreased IL-22 and IL-17A production by T-cells and reduced NLRP3 inflammasome activation 2. In intestinal tissue, IL-38 acts as a growth factor for stem cells by inducing WNT signaling through IL-1R6 binding, promoting organoid growth while maintaining homeostasis through controlled IL-1β secretion 3. IL-38 serves as a negative regulator of trained immunity, dampening excessive innate immune responses that could contribute to pathological inflammation 4. Clinically, IL-38 deficiency is associated with worse outcomes in inflammatory bowel disease and enhanced tumor susceptibility, as IL-38 blockade paradoxically improves anti-tumor immunity by activating γδ T cell-dependent responses 25. Genetic variants in IL1F10 are associated with altered cytokine production and disease susceptibility, including thyroid-associated ophthalmopathy and gout 67.