Dipeptidyl Peptidases: Substrates and Therapeutic Targeting in Human Health and Disease

Enzymatic members of the dipeptidyl peptidase (DP) 4-like gene family have been implicated in a wide range of diseases including type II diabetes, rheumatoid arthritis, wound healing and cancer. DP4 is a clinically validated target for the treatment of type II diabetes. Evidence supporting the role of DPs in immune function is increasing such that the development of further targeted therapeutics seems promising. Elucidation of DP substrates will help to reveal additional roles for this unique protease family, opening the door for further therapeutic avenues. Here, we provide an introduction to the biochemical properties of DP4, fibroblast activation protein (FAP), DP8 and DP9, and discuss their biological substrates, physiological roles, and the potential for therapeutic targeting of this family.