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. The protein encoded by this immunoglobulin superfamily gene member is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, the this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions. The encoded protein is a member of the junctional adhesion molecule protein family and acts as a receptor for another member of this family. A mutation in an intron of this gene is associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Alternative splicing results in multiple transcript variants. Diseases associated with JAM3 include Hemorrhagic Destruction Of The Brain, Subependymal Calcification, And Cataracts and Pseudo-Torch Syndrome 1. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways. An important paralog of this gene is JAM2.