Equine Interleukin-36 Receptor Antagonist (IL-36Ra) is an anti-inflammatory cytokine that regulates IL-36–mediated immune responses in horses (Equus caballus). 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, equine 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, respiratory tract, and gastrointestinal mucosa. In horses, IL-36Ra contributes to maintaining immune homeostasis and controlling excessive inflammatory responses associated with infection, tissue injury, or immune-mediated disease. In cell culture, recombinant equine 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. Equine IL-36Ra is also studied in veterinary and translational research to better understand inflammatory mechanisms in equine skin and mucosal diseases and to explore cytokine pathways that may be relevant to inflammatory disorders across species.