Nectin 2 also known as PVRL2, CD116 is a member of the nectin family, which plays a significant role in cell adhesion and communication, particularly in viral entry mechanisms. Nectin 2 is predominantly expressed in various human cell types, including neuronal cell lines, fibroblasts, keratinocytes, and activated T lymphocytes, highlighting its importance in both neural and immune responses. Nectin 2 exists in two splicing variants, Nectin 2α and Nectin 2δ, which differ in their cytoplasmic and transmembrane regions while sharing identical extracellular domains. The C-terminal conserved motif present in both variants is essential for interaction with the PDZ domain of afadin, linking Nectin 2 to the actin cytoskeleton and facilitating cellular adhesion. Nectin 2 mediates the entry of specific herpes simplex virus strains, underscoring its role in viral pathogenesis and potential implications in therapeutic strategies.