Mink/Ferret Interleukin-36 Receptor Antagonist (IL-36Ra) is an anti-inflammatory cytokine that regulates IL-36–mediated immune responses in mink (Neogale vison) and ferrets (Mustela putorius furo). The IL-36Ra protein is identical at the amino acid level in these two species, reflecting strong conservation of this regulatory cytokine within mustelids. 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, mink and ferret IL-36Ra suppress 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 and mucosal surfaces. In these species, IL-36Ra contributes to maintaining immune homeostasis and controlling excessive inflammatory responses during infection or tissue injury. In cell culture, recombinant mink/ferret 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 inflammatory pathway modulation in vitro. Mink and ferret IL-36Ra are also studied in veterinary and translational research, particularly in investigations of inflammatory and infectious diseases in mustelids and in ferret models used to study human respiratory viruses such as influenza and SARS-CoV-2.