Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the CDH2 gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multiple tissues and functions to mediate cell–cell adhesion. In cardiac muscle, Cadherin-2 is an integral component in adherens junctions residing at intercalated discs, which function to mechanically and electrically couple adjacent cardiomyocytes. Alterations in expression and integrity of Cadherin-2 has been observed in various forms of disease, including human dilated cardiomyopathy. Variants in CDH2 have also been identified to cause a syndromic neurodevelopmental disorder. Structure Cadherin-2 is a protein with molecular weight of 99.7 kDa, and 906 amino acids in length. Cadherin-2, a classical cadherin from the cadherin superfamily, is composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Cadherin-2, as well as other cadherins, interact with Cadherin-2 on an adjacent cell in an anti-parallel conformation, thus creating a linear, adhesive "zipper" between cells. Function Cadherin-2, originally named Neural cadherin for its role in neural tissue, plays a role in neurons and later was found to also play a role in cardiac muscle and in cancer metastasis. Cadherin-2 is a transmembrane, homophilic glycoprotein belonging to the calcium-dependent cell adhesion molecule family. These proteins have extracellular domains that mediate homophilic interactions between adjacent cells, and C-terminal, cytoplasmic tails that mediate binding to catenins, which in turn interact with the actin cytoskeleton. Role in development Cadherin-2 plays a role in development as a calcium dependent cell–cell adhesion glycoprotein that functions during gastrulation and is required for establishment of left-right asymmetry. Cadherin-2 is widely expressed in the embryo post-implantation, showing high levels in the mesoderm with sustained expression through adulthood. Cadherin-2 mutation during development has the most significant effect on cell adhesion in the primitive heart; dissociated myocytes and abnormal heart tube development occur. Cadherin-2 plays a role in the development of the vertebrate heart at the transition of epithelial cells to trabecular and compact myocardial cell layer formation. An additional study showed that myocytes expressing a dominant negative Cadherin-2 mutant showed significant abnormalities in myocyte distribution and migration towards the endocardium, resulting in defects in trabecular formation within the myocardium. Role in cardiac muscle In cardiac muscle, Cadherin-2 is found at intercalated disc structures which provide end-on cell–cell connections that facilitate mechanical and electrical coupling between adjacent cardiomyocytes. Within