NECTIN1 (nectin cell adhesion molecule 1) is a cell surface glycoprotein that functions primarily as a cell adhesion molecule and viral receptor. As a cell adhesion molecule, NECTIN1 mediates both homophilic and heterophilic cell-cell adhesion and localizes to adherens junctions 1. The protein serves as the major receptor for herpes simplex virus 1 (HSV-1) entry into host cells, with TMEFF1 acting as a restriction factor that interacts with NECTIN1 to impair viral entry in neurons 2. Interestingly, NECTIN1 exhibits opposing roles in different viral infections - while facilitating herpesvirus entry, it acts as a restriction factor for flaviviruses including bovine viral diarrhea virus by competing with CD46 for viral binding and inhibiting viral attachment 3. In cancer contexts, NECTIN1 functions as a tumor suppressor in melanoma, where its loss promotes tumor dissemination specifically under low IGF1 conditions 1. However, in hepatocellular carcinoma, NECTIN1 (PVRL1) is upregulated and stabilizes cell surface PVR, leading to immune evasion through TIGIT-mediated suppression of CD8+ T cells 4. NECTIN1 expression correlates with clinical outcomes in various cancers, including bladder urothelial carcinoma where it serves as a prognostic indicator 5.