IL18BP (interleukin 18 binding protein) functions as a high-affinity decoy receptor that binds to IL-18 and inhibits its biological activity, serving as a critical negative regulator of inflammatory responses 1. The protein acts as a circulating soluble inhibitor that sequesters IL-18, preventing its interaction with the IL-18 receptor and subsequent activation of Th1 immune responses 2. Mechanistically, IL18BP belongs to the IL-1 receptor family and functions as a secreted immune checkpoint that maintains immune homeostasis by controlling IL-18-mediated inflammation 3. In the tumor microenvironment, IL18BP is frequently upregulated in diverse human and mouse tumors, where it limits anti-tumor immunity by blocking IL-18's ability to promote effector CD8+ T cell development and natural killer cell activation 3. The protein plays significant roles in disease pathogenesis, particularly in hepatitis A where genetic variations in IL18BP have been linked to disease severity 4. Additionally, IL18BP expression is upregulated in immunosuppressive macrophages within glioblastoma, contributing to the dysfunctional immune microenvironment 5. Loss of IL18BP function, combined with increased IL-18 secretion, can enhance antitumor immunity by promoting CD8+ T cell cytotoxicity 6. The protein represents a therapeutic target, as engineered decoy-resistant IL-18 variants that bypass IL18BP inhibition show enhanced anti-tumor efficacy 3.