CD26 (dipeptidylpeptidase 4, adenosine deaminase complexing protein 2, ADABP, ADCP2, DPPIV, TP103) is a membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. CD26 has an essential role in immune regulation as a T cell activation molecule and a regulator of chemokine function. CD26 associates with CXCR4 and gp120 and may influence the pathophysiology of HIV infection. Adenosine deaminase (ADA) colocalizing with adenosine receptors on dendritic cells are able to interact with CD26 expressed on lymphocytes. This costimulatory signal in the immunological synapse leads to an increase in the production of the T helper 1 and proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-6. CD26 plays a role in the pathogenesis and behavior of human cancers, including solid tumors and hematological malignancies. CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on TT-loaded monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation.