CD300a is an inhibitory immunoreceptor expressed broadly on myeloid and lymphoid cells that negatively regulates immune activation through ITIM-mediated signaling 1. The receptor recognizes phosphatidylserine and phosphatidylethanolamine exposed on apoptotic cells, modulating phagocytosis by macrophages and suppressing engulfment of dead cells 2. CD300a inhibits natural killer cell cytolytic activity 1 and suppresses mast cell and basophil degranulation by downregulating IgE-mediated activation signals 3. Additionally, CD300a negatively regulates MyD88-dependent Toll-like receptor signaling 1 and modulates T cell receptor-mediated calcium mobilization in CD4+ T cells, particularly suppressing activation in Th1-polarized cells 4. Clinically, CD300a has emerged as a universal NK inhibitory target for protecting allogeneic cell therapies; engineered CD300a ligands successfully prevented NK cell-mediated rejection across diverse human donors 5. In ischemic tissue injury, CD300a deficiency enhances macrophage-mediated clearance of dead cells and promotes pro-angiogenic neutrophil responses, resulting in reduced inflammation and adverse cardiac and renal remodeling 6. CD300a expression on marginal zone B cells correlates with enhanced polysaccharide-specific IgM responses, and reduced expression in HIV-infected individuals correlates with impaired pneumococcal immunity 7.