The monoclonal antibody 6D8 recognizes the extracellular domain of human desmoglein-2. Desmogleins and desmocollins are members of the cadherin family of transmembrane proteins that together make up the core of the desmosome, a structure that provides transmembrane strength to tissues undergoing mechanical stress. The desmosomal cadherins, desmogleins and desmocollins, mediate calcium-dependent cell-cell adhesion by forming homotypic and heterotypic interactions with one another. The multiprotein desmosomal complex also includes the cytoplasmic desmosomal plaque proteins plakoglobin, phakophilins, and desmoplakin, which bind to the intracellular domain of the desmogleins and function to anchor the keratin intermediate filament network to site of cellcell contacts.In human, four desmogleins have been identified (Dsg14). Desmogleins are synthesized with a signal peptide that directs them to the endoplasmic reticulum and a proregion that is removed during protein processing. The mature protein includes four highly conserved extracellular domains (EC 14) and a fifth membrane proximal, more variable EC domain that is referred to as the “extracellular anchor domain. Desmoglein-2 is expressed on various cells including simple epithelia and myocardium, tumors and and many cell cultures.Desmogleins play critical roles in cell adhesion and skin blistering diseases, as they are the target antigens of autoimmune antibodies and bacterial toxins. Desmosomal dysfunction has been implicated in a number of diseases, including striate palmoplantar keratoderma, skin fragility, and ectodermal dysplasia, and most recently arrhythmic right ventricular cardiomyopathy (ARVC).