Desmoglein-3, also known as pemphigus vulgaris antigen (PVA), is a 130 kDa transmembrane glycoprotein that belongs to the cadherin family of calcium dependent adhesion molecules (1 - 3). Human Desmoglein-3 is synthesized with a 26 amino acid (aa) propeptide. The mature protein consists of a 566 aa extracellular domain (ECD) that contains four cadherin-like domains, a 25 aa transmembrane segment, and a 359 aa cytoplasmic domain (4). Within the ECD, human Desmoglein-3 shares 78% aa sequence identity with mouse and rat Desmoglein-3. It shares 44%, 47%, and 56% aa sequence identity with Desmoglein-1, -2, and -4 respectively. Desmoglein-3 is one of the principal components of desmosomes which form adhesive contacts between epithelial cells (1, 2). It is expressed in the basal and suprabasal layers of stratified epithelia in many tissues (4 - 6). During apoptosis, Desmoglein-3 is cleaved by caspases, plus MMP-2, and MMP-9 at sites within the cytoplasmic and extracellular regions, resulting in shortened transmembrane forms and a soluble 75 kDa ECD fragment (7, 8). The downregulation of Desmoglein-3 in oral squamous cell carcinoma correlates with metastatic potential (9). Desmoglein-3 is the target of autoantibodies in pemphigus vulgaris, a blistering skin disorder with compromised inter-keratinocyte adhesion (6, 10). Binding of these antibodies triggers Desmoglein-3 internalization and degradation by keratinocytes (10).