CD112 (also known as PVRL2 or NECTIN2) is a cell-surface protein belonging to the Nectin family of immunoglobulin-like adhesion molecules. It plays a role in cell-cell adhesion, immune regulation, and viral entry (e.g., measles virus). Structurally, it contains three extracellular Ig-like domains and interacts with multiple ligands, including CD226 (DNAM-1) on immune cells and the viral receptor CD46. In the immune context, CD112 is expressed on antigen-presenting cells, endothelial cells, and certain tumors, where it modulates T-cell and NK-cell activity via the CD226 pathway. Recent studies highlight its dual role as a potential immune checkpoint. CD112 binds to the inhibitory receptor CD112R (PVRIG), suppressing T-cell activation, while its interaction with CD226 promotes anti-tumor immunity. This balance positions CD112 as a therapeutic target in cancer immunotherapy. Antibodies targeting CD112 or its receptors aim to disrupt inhibitory signals (e.g., blocking CD112R) or enhance stimulatory pathways (e.g., engaging CD226). Preclinical models show that anti-CD112 antibodies, particularly in combination with PD-1/PD-L1 inhibitors, can enhance T-cell infiltration and tumor control. Ongoing research explores its clinical potential, biomarker relevance, and synergy with existing immunotherapies.