DSC2 (desmocollin 2) is a calcium-binding cadherin that functions as a core structural component of desmosomes, the cell-cell junctions essential for epithelial integrity 1. DSC2 promotes timely incorporation of desmogleins into desmosomal junctions and facilitates interaction between desmosomes and intermediate filament networks through modulation of desmoplakin phosphorylation 2. In the intestinal epithelium, DSC2 maintains barrier function and intercellular adhesion strength while positively regulating wound healing through promotion of epithelial cell migration and mechanotransduction 3. Clinically, DSC2 variants are a leading cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited disorder characterized by right ventricular dysplasia and life-threatening arrhythmias 34. Loss-of-function DSC2 mutations cause ARVC through impaired desmosomal function; mechanistic studies reveal that DSC2 deficiency reduces expression of Myl7 (myosin light chain 2a), contributing to cardiac contractility deficits 5. Multiple DSC2 variants are associated with earlier disease onset, more severe biventricular dysfunction, and increased risk of end-stage heart failure compared with single-variant carriers 3. Notably, DSC2 serves as the principal epithelial entry receptor for Epstein-Barr virus, facilitating infection through direct interaction with viral gH/gL glycoproteins 67. mRNA-based therapeutic approaches show promising restoration of cardiac function in DSC2-deficient mouse models 5.