DSG3

Desmoglein-3 (DSG3) is a transmembrane glycoprotein that belongs to the desmoglein subfamily of cadherins, and it is encoded by the DSG3 gene in humans. It is a component of desmosomes, cellular structures that mediate strong cell–cell adhesion in epithelial tissues. The protein has multiple extracellular cadherin repeats that mediate calcium-dependent adhesion between neighboring cells, and a cytoplasmic tail that associates with desmosomal plaque proteins such as desmoplakin and plakophilins, linking the desmosome to the intermediate filament cytoskeleton.

DSG3 is predominantly expressed in stratified squamous epithelia, including the oral mucosa, esophagus, and other mucosal surfaces, with varying levels in different tissues of the skin and mucosa. Its proper function supports cohesive epithelial layers; loss or disruption of DSG3 can weaken cell–cell adhesion and promote acantholysis, a hallmark of desmosomal disorders.

Clinically, DSG3 is best known for its role in pemphigus vulgaris, an autoimmune blistering disease. Autoantibodies against Dsg3 can disrupt desmosomal adhesion, leading to mucosal erosions, with skin involvement depending on the presence of autoantibodies to other desmogleins (notably Dsg1). Diagnostic testing often includes assays that detect anti-DSG3 antibodies and immunofluorescence to demonstrate intercellular staining in lesional tissue.

Beyond autoimmune disease, DSG3 expression has been investigated in cancer biology. It is sometimes upregulated in squamous cell carcinomas and can serve as an immunohistochemical marker in diagnostic pathology, supporting tumor classification and, in some contexts, providing prognostic information.