Dipeptidyl peptidase 4 family (DPP-4 family)

The dipeptidyl peptidase 4 (DPP-4) family of proteases, also known as the S9B family of serine peptidases, consists of enzymes that specifically cleave dipeptides from the N-terminus of proteins, typically after a proline or alanine residue (PMID: 29405165). The most prominent member, DPP-4 (also known as CD26), plays a critical role in glucose homeostasis by inactivating incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (StatPearls: NBK526010). Other members of the family include fibroblast activation protein (FAP), DPP-8, and DPP-9, which are involved in tissue remodeling, immune regulation, and intracellular signaling (UniProt: P27487). In clinical practice, DPP-4 is a major therapeutic target for the treatment of type 2 diabetes mellitus, where inhibitors (gliptins) are used to prolong the half-life of endogenous incretins (PubMed: 30115462). Beyond metabolic control, these proteases are investigated for their roles in oncology, particularly FAP in the tumor microenvironment, and in inflammatory conditions (PMID: 31433957). Selective inhibition is a key pharmacological goal to avoid toxicity associated with the inhibition of intracellular family members like DPP-8 and DPP-9 (PubMed: 16172273).

Other names

Dipeptidyl peptidase IV familyS9B familyCD26 familyProlyl oligopeptidase family

Inhibition of dipeptidyl peptidase 4 activity to prevent the degradation of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), leading to enhanced insulin secretion and suppressed glucagon release in a glucose-dependent manner (StatPearls: NBK526010).