Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. Involved in the formation and regulation of the tight junction (TJ) paracellular permeability barrier in epithelial cells (PubMed:16188940). Plays a role in VAMP3-mediated vesicular transport and recycling of different receptor molecules through its interaction with VAMP3 (PubMed:20057356). Plays a role in the regulation of cell shape and movement by modulating the Rho-family GTPase activity through its interaction with ARHGEF25/GEFT (PubMed:18541910). Induces primordial adhesive contact and aggregation of epithelial cells in a Ca(2+)-independent manner. Also involved in striated muscle regeneration and repair and in the regulation of cell spreading (PubMed:11839816). Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density (PubMed:26642364). Is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity as well as for heart protection against ischemia injury (PubMed:24066022). Homodimer. Homodimerization requires the C-terminus cytoplasmic region (By similarity). Interacts (via the C-terminus cytoplasmic tail) with TJP1. Interacts (via the C-terminus cytoplasmic tail) with ARHGEF25/GEFT (via the DH domain). Interacts (via the C-terminus cytoplasmic tail) with VAMP3. Interacts with KCNK2; the interaction enhances KCNK2 surface expression and is inhibited by cAMP (PubMed:22354168, PubMed:26642364). Interacts with CAV3 (PubMed:24066022). Its movement from the cytoplasm to membrane is an early event occurring concurrently with cell-cell contact. Detected at cell-cell contact but never observed at the free surface of epithelial cells (By similarity). Colocalizes in epithelial cells with OCLN and TJP1 in an apical-lateral position within the z axis. Colocalizes with VAMP3 at the cell-cell contact in cardiac and skeletal muscle. Expressed in epithelial cells, skeletal muscle, heart and intestinal smooth muscle (at protein level). Expressed in fetal and adult heart and skeletal muscle. Expressed in the mesoderm of the cardiac crescent at 9.5 dpc. Expressed in cardiac myocytes of the sinoatrial compartment and some restricted areas of the dorsal part of the ventricle chambers at 10.5 dpc and 12.5 dpc. Expressed in branchial arches, myotome and in a posterior domain in the limb at 10.5 dpc. Expressed in the heart, mainly in the compact layer myocardium, peridigital mesenchyme, the somites of the tail bud, the smooth muscle cells of the trachea and the developing bronchial tree, the smooth muscle cells lining the digestive tract, the dorsal root ganglia and the pancreas anlage at 13.5 dpc (at protein level). Expressed in the sinoatrial compartment and some restricted areas in the dorsal part of the ventricle at 9.5 dpc, 10.5 dpc and 11.5 dpc. At 12.5 dpc, expression was observed in the ventral half of the ventricle where it was limited to the subepicardial compact layer. Skeletal muscle regeneration appears to be less efficient and delayed (PubMed:11839816). Knockout mice are deficient to adapt heart rate to physiological stress, this deficiency develops in older mice. They show severe sinus node dysfunction with long pauses and intercurrent periods of normal synus rhythm. The sinus node structure is abnormal with a loss of pacemaker tissue from the inferior part of the sinus node and a compact structure of the superior sinus node (PubMed:22354168). They have inpaired functional recovery after ischemia/reperfusion injury (PubMed:24066022). Belongs to the popeye family.