Human Interleukin-36 Receptor Antagonist (IL-36Ra) is an anti-inflammatory cytokine that regulates IL-36–mediated immune responses in humans (Homo sapiens). IL-36Ra is a member of the IL-1 cytokine family and functions as a natural inhibitor of the IL-36 signaling pathway by binding to the IL-36 receptor (IL-36R, also known as IL1RL2) without activating it, thereby preventing proinflammatory cytokines such as IL-36α, IL-36β, and IL-36γ from initiating downstream signaling. Through this mechanism, human IL-36Ra suppresses activation of intracellular pathways including NF-κB and MAPK, helping to limit production of inflammatory mediators and regulate immune responses at epithelial barrier tissues such as the skin, lungs, and gastrointestinal tract. In humans, IL-36Ra plays a critical role in maintaining immune homeostasis and preventing excessive inflammatory responses. Dysregulation or genetic deficiency of IL-36Ra has been associated with inflammatory conditions such as generalized pustular psoriasis. In cell culture, recombinant human IL-36Ra is commonly used to inhibit IL-36–induced inflammatory signaling in epithelial and immune cells, enabling investigation of cytokine regulation, epithelial–immune cell interactions, and modulation of inflammatory pathways in vitro.