Junctional adhesion molecule (JAM) is a member of the immunoglobulin superfamily expressed in tight junctions of epithelial cells and endothelial cells. It is implicated in transendothelial migration of leukocytes. JAM is constitutively expressed on circulating monocytes, neutrophils, lymphocyte subsets and platelets. The JAM family consists of JAM-A, JAM-B and JAM-C, alternatively designated JAM-1, JAM-2 and JAM-3, respectively. JAM-A localizes with F-Actin at the cell-cell contacts and at the membrane ruffles. It is involved in cell to cell adhesion through homophilic interactions and plays a role in the organization of tight junctions and modulation of leukocyte extravasation. JAM-B interacts with discrete subsets of PBLs, suggesting that it may play a role in lymphocyte trafficking. JAM-B and JAM-C proteins are binding partners; JAM-C may be a functional JAM-B receptor. Specifically, JAM-B adheres to T cells through heterotypic interactions with JAM-C. The JAM-B/JAM-C interaction my play a role in T, NK and dendritic cellular inflammation.