Overview of Endomucin in Vascular Homeostasis and Disease

Endomucin (EMCN), a highly glycosylated type I transmembrane sialomucin, is predominantly expressed on the luminal surface of venous and capillary endothelial cells and serves as a critical guardian of vascular homeostasis and immunological silencing. Its highly extended, O-glycosylated extracellular domain provides significant steric hindrance and electrostatic repulsion, functioning as a dual physical barrier that prevents nonspecific leukocyte tethering and adhesion. Beyond its anti-adhesive role, EMCN is a pivotal orchestrator of angiogenesis, modulating the vascular endothelial growth factor signaling cascade by facilitating vascular endothelial growth factor receptor 2 autophosphorylation at the Y1175 residue and subsequent receptor internalization. Furthermore, EMCN has emerged as a specialized marker for type H vessels and human hematopoietic stem cells, playing indispensable roles in vessel-bone coupling and hematopoietic development. Clinical evidence indicates that the dysregulation of EMCN expression or post-translational modifications contributes to the pathogenesis of diabetic complications, atherosclerosis, bone metabolic disorders, and tumor metastasis. This review systematically summarizes structural characteristics, expression patterns, and multifaceted biological functions of EMCN, providing a theoretical foundation for the development of novel therapeutic strategies for microvascular and metabolic diseases.