CD26 is a signal-anchor for type II membrane protein that belongs to the peptidase S9B family. CD26 is expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. It acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. It’s binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. It may be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, it enhanced cell proliferation, a process inhibited by GPC3. It acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones.