LILRB2 is an inhibitory immune checkpoint receptor that functions as a negative regulator of immune responses through recognition of HLA class I molecules. The receptor binds to a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G, and HLA-F alleles, with HLA-G recognition triggering differentiation of regulatory T cells and myeloid-derived suppressor cells that maintain maternal-fetal tolerance 1. LILRB2 contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and inhibits immune cell activation by competing with CD8A for MHC class I binding and suppressing calcium mobilization and protein phosphorylation. In microglia, LILRB2 negatively regulates TREM2 signaling through shared ligand binding to oligomeric amyloid-β, inhibiting microglial phagocytosis, migration, and inflammatory responses 2. The receptor plays pathological roles in multiple diseases: it promotes macrophage recruitment in non-alcoholic steatohepatitis through ANGPTL8 binding 3, enhances tumor immune evasion and radiation resistance in NSCLC via JAK2/STAT3 pathway activation 45, and contributes to pathological myopia development through promotion of fatty acid synthesis and lipid accumulation 6. LILRB2 represents a promising therapeutic target, as its inhibition can enhance anti-tumor immunity and improve treatment responses in cancer and potentially other diseases.