LILRB4 is an inhibitory immunoglobulin-like receptor that functions as a key negative regulator of immune responses across multiple cell types and disease contexts. As an immune checkpoint molecule expressed on myeloid cells and leukemic blasts, LILRB4 suppresses T cell proliferation and cytotoxic differentiation while promoting immune tolerance 1. The receptor mediates inhibitory signaling through multiple ligands including apolipoprotein E, fibronectin, secretogranin 2, and ALCAM, triggering SHP-2-dependent phosphatase cascades that reduce phosphorylation of signaling proteins and dampen calcium mobilization 12. In monocytes, LILRB4 engagement suppresses Fc receptor-mediated activation and TNF production 1. LILRB4 has emerged as a critical therapeutic target in hematologic and solid malignancies. In acute myeloid leukemia, LILRB4 orchestrates tumor cell invasion and creates an immunosuppressive microenvironment 1. High LILRB4 expression on multiple myeloma cells correlates with poor prognosis and drug resistance, while promoting myeloid-derived suppressive cell function 3. In Alzheimer's disease, microglial LILRB4 suppresses amyloid-β clearance through ApoE binding; anti-LILRB4 antibodies enhance microglial activity and reduce amyloid pathology 4. LILRB4-targeted therapies, including monoclonal antibodies and CAR-T cell approaches, show promise for restoring anti-tumor and anti-pathogen immunity.