Prolidase (Peptidase D) (PEPD)

Prolidase (Peptidase D) is a ubiquitous cytosolic metalloenzyme that plays a critical role in the final stages of protein catabolism, specifically the recycling of proline from collagen [1, 4]. It is the only human enzyme capable of cleaving imidodipeptides containing C-terminal proline or hydroxyproline residues, making it the rate-limiting step in extracellular matrix remodeling and wound healing [1, 6]. Clinically, mutations in the PEPD gene cause prolidase deficiency, a rare autosomal recessive disorder characterized by recalcitrant skin ulcers, intellectual disability, and immune system abnormalities [7, 10]. Beyond its catalytic function, prolidase serves as a regulatory protein that can bind to receptors like EGFR and HER2, influencing cell growth and metabolism [3]. In oncology, prolidase is frequently upregulated to support the high demand for proline during tumor progression, positioning it as a potential therapeutic target for enzyme inhibitors [5, 11]. Current research explores its utility as a clinical biomarker for disease severity and the development of recombinant prolidase for enzyme replacement therapy [9, 12].

Other names

X-Pro dipeptidaseXaa-Pro dipeptidaseProline dipeptidaseImidodipeptidasePeptidase D

Hydrolysis of imidodipeptides with a C-terminal proline or hydroxyproline to provide free proline for protein synthesis; enzyme replacement or cofactor supplementation to restore catalytic activity; inhibition of enzymatic activity to disrupt collagen turnover in cancer cells [1, 5, 9, 12].