Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a cell surface glycoprotein receptor and serine exopeptidase that plays a multifaceted role in immune regulation, signal transduction, and glucose metabolism. DPP4 is essential for T-cell receptor (TCR)-mediated T-cell activation by acting as a costimulatory molecule. It interacts with various proteins, including ADA, CAV1, IGF2R, and PTPRC, to promote T-cell coactivation, proliferation, and NF-κB activation. Additionally, DPP4 regulates lymphocyte-epithelial cell adhesion and is involved in pericellular proteolysis of the extracellular matrix (ECM), facilitating endothelial cell migration and invasion. DPP4 exhibits dipeptidyl peptidase activity, cleaving N-terminal dipeptides from polypeptides with proline or alanine at the penultimate position. This activity modulates the biological activity of various substrates, including chemokines, growth factors, neuropeptides, and peptide hormones. For example, DPP4-mediated cleavage of incretins like GLP-1 impacts glucose metabolism, while cleavage of chemokines such as RANTES alters receptor binding specificity. DPP4 is also implicated in tumor suppression and lymphatic endothelial cell functions, including adhesion, migration, and tube formation. Furthermore, it serves as a receptor for human coronavirus MERS-CoV, highlighting its role in viral pathogenesis.