CD300C is a transmembrane signaling receptor belonging to the CD300 family of paired immune receptors, with expression primarily on monocytes, mast cells, basophils, and professional antigen-presenting cells 1. Unlike its homologous inhibitory counterpart CD300A, CD300C functions as an activating receptor that delivers Fc receptor-γ-dependent signals 1. CD300C recognizes phosphatidylethanolamine (PE) and apoptotic cells as ligands, though with lower affinity than CD300A 1. The receptor acts as a costimulatory molecule during IgE-mediated basophil activation, enhancing degranulation and cytokine production 2. Beyond innate immunity, CD300C functions as a novel B7-family T cell co-inhibitory molecule expressed on antigen-presenting cells, with its counter-receptor upregulated on activated CD4 and CD8 T cells 3. CD300C-Fc fusion protein significantly attenuates both graft-versus-host disease and collagen-induced arthritis in mice by suppressing T cell proliferation and reducing proinflammatory cytokine production 34. Additionally, CD300C-specific monoclonal antibodies promote M1 macrophage differentiation through MAPK and NF-κB signaling, suggesting immunooncology applications 5. CD300C expression is elevated in cow's milk allergy patients and correlates with symptom severity 2. Recent proteomic analyses identified CD300C as a novel protein associated with chr17 kidney disease in individuals with abnormal glucose metabolism 6.