IL-36α is one of the IL-36 cytokines that are part of the IL-1 family. Like other IL-1 family members, IL-36α requires N-terminal processing to gain full bioactivity. IL-36α signals through IL-36R/IL-1RAcP, which results in MAPK, Erk1/2, and JNK activation. IL-36α is implicated in skin homeostasis, and is overexpressed in psoriatic lesional skin. Transgenic mice overexpressing IL-36α in their skin have an inflammatory skin condition showing some characteristics of human psoriasis, including thickened scaly skin, acanthosis, hyperkeratosis, and dermis infiltration. EGF regulates expression of IL-36α in skin cells. IL-36α can also be detected in adipose tissue where it reduces adipocyte differentiation and also induces inflammatory gene expression in mature adipocytes. In lungs, the expression of IL-36α is increased in response to inflammatory stimuli. Intratracheal instillation of recombinant mouse IL-36α induces CXCL1 and CXCL2 expression and also neutrophil influx in the lungs. IL-36α, IL-36β, and IL-36γ induce in vitro expression of RNAs of multiple cytokines (IL-6, IL-12 p40, CXCL1, CCL1, IL-12 p35, IL-1β, IL-19 p19, GM-CSF, CXCL10, TNFα, CCL3, VCAM-1, and ICAM-1) in mouse bone marrow-derived dendritic cells and CD4 T cells obtained from normal mice. IL-36α expression is elevated in chronic kidney disease and in rheumatoid arthritis synovium, and decreased expression correlates with a poor prognosis in hepatocellular carcinomas.