Desmoglein 2 (DSG2) (DSG2)

Desmoglein 2 (DSG2) is a calcium-binding transmembrane glycoprotein belonging to the cadherin superfamily and is a fundamental component of desmosomes, which provide mechanical cohesion to epithelial and cardiac tissues (UniProt P15924). Beyond its structural role, DSG2 acts as a signaling scaffold and is a primary high-affinity receptor for several species B adenoviruses, including Ad3, Ad7, Ad11, and Ad14 (Nature Medicine 2011; 17(1):96-104). In oncology, DSG2 is frequently overexpressed in epithelial malignancies, making it a target for oncolytic adenoviruses like Ad5/3-E2F-d24-hIL2. This specific virus utilizes a chimeric fiber knob to facilitate tumor-selective entry and delivery of therapeutic payloads such as interleukin-2. Binding to DSG2 can trigger "junction opening," which enhances the intratumoral penetration of the virus and co-administered chemotherapeutics. However, therapeutic targeting of DSG2 requires careful monitoring due to its critical role in the heart; mutations or dysfunction in DSG2 are primary causes of arrhythmogenic right ventricular cardiomyopathy (ARVC) (PubMed: 16415888). Thus, while DSG2 is a promising portal for cancer therapy, its systemic modulation poses risks to cardiac and epithelial integrity.

Other names

CDHF5Cadherin family member 5HDGC

Acts as a high-affinity attachment receptor for species B adenoviruses; facilitates viral entry and triggers intercellular junction remodeling to enhance therapeutic penetration.