CXADR (Coxsackievirus and Adenovirus Receptor) is a multifunctional immunoglobulin superfamily cell adhesion molecule with diverse tissue-specific roles. Primarily, CXADR serves as a viral receptor for Coxsackievirus B1-B6 1 and functions as a junction structural protein and signaling molecule 1. The protein localizes to apicolateral and basolateral plasma membranes, where it mediates cell-cell adhesion through heterophilic interactions and integrin binding 1. CXADR regulates multiple cellular processes including leukocyte transmigration, barrier function, cell adhesion, and epithelial-mesenchymal transition (EMT) 1. Mechanistically, CXADR controls EMT through the AKT/GSK-3β signaling axis, modulating PHLPP2 and PTEN-mediated AKT phosphorylation to regulate SNAIL1 stability 2. During placental development, CXADR functions as a fate determinant regulating differentiation dynamics between syncytiotrophoblast layers 3. In erythroid lineages, CXADR promotes differentiation and migration of erythroid progenitors 4. Clinically, CXADR downregulation associates with myelodysplastic syndromes (MDS), correlating with high-risk disease and decreased survival 4. In colorectal cancer, CXADR exhibits tumor-suppressive function through mTOR-AKT-β-catenin pathway regulation 5. CXADR expression correlates with advanced head and neck squamous cell carcinoma stage and positive HPV status 6, suggesting therapeutic potential for adenoviral vector-based treatments.