VE-Cadherin (Vascular Endothelial Cadherin, CDH5) is an endothelial-specific transmembrane adhesion protein of the Cadherin superfamily that is essential for the formation and maintenance of adherens junctions between endothelial cells (1–3). It is expressed predominantly in vascular endothelial cells, where it mediates calcium-dependent homophilic cell-cell adhesion and helps preserve vascular integrity, barrier function, and endothelial survival (1–4). As a junctional protein, VE-Cadherin interacts through its cytoplasmic domain with Catenins such as β-Catenin, p120-Catenin, and plakoglobin, thereby linking endothelial junctions to the actin cytoskeleton and intracellular signaling pathways (3,5). Through these structural and signaling functions, VE-Cadherin plays a central role in regulating junction stability, vascular permeability, and endothelial homeostasis (1,2,8,9). VE-Cadherin carries multiple N and O glycosylation sites that modulate its folding, surface expression, and interaction with Catenins.
In vascular tissues, VE-Cadherin is closely associated with the control of endothelial barrier function, angiogenesis, and inflammatory responses (1,2,6,8). Disruption of VE-Cadherin-mediated adhesion leads to increased vascular permeability and contributes to edema, leukocyte transmigration, and vessel destabilization during inflammation and disease (1,2,6). VE-Cadherin is also required for proper vascular morphogenesis and endothelial cell survival during development, highlighting its essential role in blood vessel formation and remodeling (4,7). Because of its endothelial-restricted expression and its importance in vascular biology, VE-Cadherin is widely used as a marker of endothelial cells and as a key mediator of vascular dysfunction in disorders such as inflammation, tumor angiogenesis, and other diseases associated with impaired vessel stability (1,2,7–9).
