VE-Cadherin, also known as Cadherin-5 and CD144, is a member of the atypical/type II subgroup of Cadherin homophilic adhesion proteins. A 90 kDa portion of the VE-Cadherin ECD can be shed in a metalloproteinase-dependent mechanism and may function as a VE-Cadherin antagonist. VE-Cadherin is expressed on the surface of vascular endothelial cells (EC) from early in embryogenesis through adulthood as well as in the placenta, on hematopoietic cell progenitors, and on a subpopulation of hematopoietic stem cells. It is a major protein component of adherens junctions between cells of the endothelium. VE-Cadherin supports the extension and stabilization of existing vascular sprouts. VE-Cadherin also regulates or is regulated by VEGF R2, type I and type II TGF-beta receptors, and other endothelial junction proteins such as JAM-C, Claudin-5, and N-Cadherin. Elevated levels of soluble VE-Cadherin are found in the serum of myocardial infarction, angina pectoris, rheumatoid arthritis, and colorectal cancer patients.