CD300LF is an inhibitory immunoreceptor that serves multiple critical roles in immune regulation and viral pathogenesis. Functionally, CD300LF acts as a phospholipid-binding receptor that recognizes phosphatidylserine (PS) on apoptotic cells to promote macrophage-mediated efferocytosis while inhibiting dendritic cell-mediated clearance, thereby maintaining immune homeostasis 1. Additionally, CD300LF binds ceramide and sphingomyelin to suppress mast cell activation and allergic responses via FcεRI inhibition 1. Mechanistically, CD300LF negatively regulates Toll-like receptor signaling by activating phosphatase PTPN6/SHP-1, dampening inflammatory responses 2. CD300LF has emerged as the primary physiologic receptor for murine norovirus (MNoV), with expression on intestinal epithelial cells and tuft cells being essential for persistent strain transmission 34. Notably, human CD300LF does not serve as a receptor for human norovirus, indicating species-specific tropism 3. Clinically, CD300LF dysfunction is associated with periodontitis pathogenesis. CD300LF downregulation accelerates neutrophil aging, increasing reactive oxygen species and pro-inflammatory mediators like IL-1β and S100A8/A9 2. CD300LF signaling in monocytes/macrophages promotes anti-inflammatory M2-type differentiation and PD-L1 upregulation, suggesting therapeutic potential in cancer immunotherapy 5.