The zonula occludens proteins (ZOPs), ZO-1, ZO-2 and ZO-3 are tight-junction phosphorylated proteins that belong to the membrane-associated guanylated kinase (MAGUK) family. ZOs are involved in the organization of epithelial and endothelial intercellular junctions and bind to the cytoplasmic C-termini of junctional transmembrane proteins linking them to the actin cytoskeleton, ZOPs contain three PDZ domains, one SH3 domain, and a guanylate kinase-like domain, indicating that ZOPs may serve multiple purposes. ZOPs contain some unique motifs not shared by other MAGUK family members, including nuclear localization and nuclear export signals and a leucine zipper-like sequence. Their potential involvement in cell growing and proliferation has been suggested based on the observation that the N-terminal half of ZOPs displays a significant similarity to the product of the Drosophila tumor suppressor gene lethal disc-large (dlg).