X-prolyl aminopeptidase 2 (XPNPEP2) (XPNPEP2)

X-prolyl aminopeptidase 2 (XPNPEP2), also known as membrane-bound aminopeptidase P (AP-P2), is a zinc-dependent metalloprotease anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) bridge (UniProt: O43895; GeneCards: XPNPEP2). It plays a critical role in the degradation of vasoactive peptides, most notably bradykinin and its active metabolite des-Arg9-bradykinin, by cleaving the N-terminal amino acid from peptides with a proline residue at the second position (PubMed: 15361070). This enzyme is a key component of an alternative pathway for bradykinin metabolism, which becomes particularly important when the primary degradation enzyme, angiotensin-converting enzyme (ACE), is inhibited (PMC: 1275611). Genetic variations in XPNPEP2, such as the C-2399A polymorphism, are strongly associated with reduced enzymatic activity and an increased risk of life-threatening ACE inhibitor-induced angioedema (PubMed: 11586201). Beyond its role in cardiovascular homeostasis, XPNPEP2 has been implicated in cancer progression, where its upregulation promotes epithelial-mesenchymal transition and metastasis in cervical and prostate cancers (GeneCards: XPNPEP2). While no drugs targeting XPNPEP2 are currently approved for clinical use, experimental inhibitors like apstatin have been studied for their potential cardioprotective effects, and the enzyme remains a subject of interest for both safety screening and oncology therapeutics (PubMed: 10395490).

Other names

Aminopeptidase P2Membrane-bound aminopeptidase PmAmPAPP2X-Pro aminopeptidase 2X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-boundAEACEI

Inhibition of the metalloprotease active site to prevent the degradation of bradykinin and other proline-containing peptides.