Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmoglein subfamily of cadherins, primarily involved in cell-cell adhesion through desmosomes—specialized intercellular junctions critical for tissue integrity. Expressed ubiquitously in epithelial and myocardial tissues, DSG2 plays a vital role in maintaining structural stability and mechanical resilience in tissues subjected to stress, such as the skin, heart, and gastrointestinal tract. Beyond its structural function, DSG2 participates in signaling pathways regulating cell proliferation, differentiation, and apoptosis, linking it to pathological processes like cancer progression and cardiovascular diseases.
DSG2 antibodies, either autoantibodies or research tools, have significant clinical and experimental relevance. In autoimmune disorders like paraneoplastic pemphigus or arrhythmogenic cardiomyopathy, autoantibodies against DSG2 disrupt desmosomal adhesion, leading to tissue blistering or myocardial dysfunction. In cancer research, DSG2 overexpression is observed in certain carcinomas (e.g., gastric, colorectal), and DSG2-targeting antibodies are explored for diagnostic or therapeutic purposes. For example, monoclonal antibodies against DSG2 are studied for their potential to inhibit tumor growth or enhance drug delivery by binding overexpressed DSG2 on cancer cells.
However, DSG2 antibodies also pose challenges. Their cross-reactivity with other desmogleins or unintended tissues may complicate therapeutic applications. Additionally, cardiac toxicity risks limit the use of DSG2-targeting agents due to the protein’s critical role in myocardial integrity. Ongoing research aims to refine antibody specificity and evaluate their dual role as biomarkers and therapeutic targets in diseases linked to desmosomal dysfunction.