E-cadherin, also known as cadherin-1, CDH1 and CD324, is a member of the cadherin superfamily. E-cadherin is widely expressed in epithelial cells. It is a calcium-dependent, transmembrane cell-cell adhesion glycoprotein composed of four extracellular cadherin repeats and a highly conserved cytoplasmic tail region. E-cadherin functions as a cell adhesion molecule involved in development, bacterial pathogenesis, and tumor invasion. E-cadherin forms homophilic clusters via cis and trans interaction to stabilize the catenin and actin cytoskeleton in epithelial adherens junctions. E-cadherin and α-catenin can form the distinct complexes with β-catenin and plakoglobin, respectively. Mice lacking E-cadherin in the epidermis leads to perinatal death and loss of barrier function. Regulating E-cadherin turnover is essential to modulate epithelial plasticity during tissue remodeling and stretching. In bacterial pathogenesis, the ectodomain of E-cadherin mediates bacterial adhesion to mammalian cells, while the cytoplasmic domain is required for internalization. E-cadherin binds to the αEβ7 integrin to mediate cell adhesion. It also interacts with a number of intracellular proteins including including erbin, ezrin, caspase-3, caspase-8, β-catenin, presenilin 1, and casein kinase II as well as other extracellular proteins including the EGF receptor. E-cadherin is phosphorylated on multiple residues (S857, S866, S870, S872), and can be proteolytically cleaved at residue D769 by caspase-3. There are several diseases associated with dysregulation of E-cadherin, including Hailey-Hailey disease and Blepharocheilodontic syndrome 1 (BCDS1).