Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. JAM3 is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions.