IL18R1 encodes the binding chain of the interleukin-18 receptor complex, responsible for recognizing the pro-inflammatory cytokine IL-18 but not IL-1A or IL-1B. Upon IL-18 binding, IL18R1 heterodimerizes with IL18RAP to recruit downstream signaling machinery including IRAK and TRAF-6, activating NF-κB-dependent gene expression and promoting interferon-gamma production from T-helper 1 cells and natural killer cells. This receptor mediates both innate and adaptive immune responses, with IL-18 signaling regulating T-cell activation, cytokine production, and immune cell infiltration in tissue microenvironments. IL18R1 dysfunction is implicated in multiple inflammatory and neoplastic diseases. In lung squamous cell carcinoma, IL18R1 downregulation is associated with reduced cytotoxic T-cell infiltration and poor prognosis 1. Conversely, aberrant IL-18 pathway activation promotes tumor immune evasion; the adaptor protein ACSL6 phosphorylates and stabilizes the IL18R1–IL18RAP heterodimer to enhance NF-κB signaling and recruit immunosuppressive myeloid cells, an effect reversed by anti-PD-1 therapy 2. IL18R1 expression is elevated in uncontrolled or severe asthma and associated with worse prognosis in idiopathic pulmonary fibrosis 3, while IL18R1 genetic variants modulate COPD susceptibility 4 and coal workers' pneumoconiosis development 5. IBOCTADEKIN, an IL-18 antagonist targeting this pathway, represents an emerging therapeutic approach for IL-18-driven pathology.