IL1R2 is a non-signaling decoy receptor that negatively regulates interleukin-1 signaling through competitive inhibition and metabolic modulation. IL1R2 preferentially binds IL1B and prevents its interaction with the signaling receptor IL1R1, thereby attenuating IL1-mediated inflammatory responses 1. Both membrane-bound and secreted forms of IL1R2 function as inhibitors; the secreted IL1R2 recruits IL1RAP with high affinity to form neutralizing complexes 2. Beyond classical receptor antagonism, IL1R2 regulates cell metabolism by directly binding enolase 1 (ENO1) to suppress glycolysis and glycolysis-mediated pyroptosis in macrophages 3. IL1R2 is clinically relevant across multiple disease contexts. In sepsis, elevated soluble IL1R2 correlates with immune dysregulation; IL1R2-deficient mice show heightened sepsis susceptibility with increased inflammation and mortality 3. IL1R2+ immature neutrophils are enriched in septic patients with poor outcomes, associated with emergency granulopoiesis and immunosuppression 4. In triple-negative breast cancer, IL1R2 activation by macrophage-derived IL1B promotes PD-L1 upregulation and CD8+ T-cell exhaustion; IL1R2 blockade combined with anti-PD-1 therapy reduces tumor burden and enhances immunotherapy efficacy 5. High IL1R2 expression in tumor-infiltrating regulatory T cells correlates with poor prognosis in lung adenocarcinoma 6. IL1R2+ neutrophils induced by chr2 stress promote breast cancer lung metastasis 7, while dexamethasone upregulates IL1R2+ neutrophils during severe COVID-19 8.