LILRB3 (leukocyte immunoglobulin-like receptor B3) is an immunomodulatory receptor primarily expressed on myeloid cells that functions as an inhibitory immune checkpoint molecule. The protein contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail that mediate inhibitory signaling 1. LILRB3 serves as a specific cell surface receptor for APOE4, forming a hetero-tetrameric complex that activates microglia into a pro-inflammatory state, which may have implications for Alzheimer's disease pathogenesis 2. In cancer contexts, LILRB3 supports immunosuppressive activity of myeloid-derived suppressor cells and tumor development, with blockade of LILRB3 signaling showing potential as a novel immunotherapy approach for solid cancers 3. The receptor also regulates acute myeloid leukemia progression by controlling cell proliferation and differentiation, with LILRB3 blockade inhibiting leukemia growth and serving as an effective target for CAR T-cell therapy 4. Clinically, genetic variants in LILRB3 are associated with kidney transplant failure in African American recipients and progression of end-stage renal disease 5. The gene exhibits high polymorphism and is linked to inflammatory bowel disease susceptibility 6. LILRB3 represents a promising therapeutic target for multiple immune-related diseases through its role in regulating myeloid cell function and immune suppression.