IL18R1 (interleukin-18 receptor 1) is a cell surface receptor that forms a complex with IL18RAP to bind the pro-inflammatory cytokine IL-18, but not IL-1A or IL-1B 1. As part of the IL-18 receptor complex, IL18R1 mediates IL-18 signaling through NF-κB activation 2, promoting interferon-gamma (IFN-γ) synthesis in T-helper 1 (Th1) cells and NK cells 3. This pathway enhances adaptive immune responses and cytokine production, including TNF, IL-1, and chemokines 2. Clinically, IL18R1 expression is significantly reduced in lung squamous cell carcinoma and inversely correlates with cancer progression, metastasis, and poor prognosis 4. IL18R1 downregulation associates with decreased CD8+ T cell infiltration and cytotoxic immunity 4. Conversely, aberrant IL-18R1 activation in hepatocellular carcinoma facilitates tumor immune evasion through ACSL6-mediated NF-κB signaling, promoting neutrophil and macrophage recruitment while inhibiting CD8+ T cell activity 5. IL18R1 is also a biomarker for asthma severity and idiopathic pulmonary fibrosis prognosis 6, with genetic variants associated with altered IFN-γ responses to vaccination 7 and COPD susceptibility 8. These findings establish IL18R1 as a critical immunomodulatory receptor with dual roles in protective and pathological immune responses.