PEPD (peptidase D) is a dipeptidase that catalyzes hydrolysis of dipeptides with C-terminal prolyl or hydroxyprolyl residues, with Gly-Pro as the preferred substrate 1. The enzyme plays a critical role in collagen metabolism by degrading proline-containing dipeptides 2, addressing the high iminoacid content in collagen 3. Mechanistically, PEPD functions both intracellularly for collagen turnover and extracellularly as a secreted protein. In obesity, decreased intracellular PEPD activity in adipose tissue macrophages paradoxically occurs alongside increased systemic PEPD secretion 2. Secreted PEPD enhances fibro-inflammatory responses via EGFR signaling, promoting adipose tissue fibrosis and insulin resistance 2. PEPD is also implicated in insulin-glucose signaling pathways that affect cardiometabolic outcomes 4. Clinically, PEPD shows relevance to multiple conditions. Prolidase deficiency, caused by PEPD gene mutations, is a rare autosomal recessive disorder characterized by skin lesions, respiratory infections, immunodeficiency, and cognitive impairment 5. Additionally, PEPD levels continuously decrease before Parkinson's disease onset and are incorporated into predictive biomarker models for PD risk stratification 6, suggesting emerging importance as a disease biomarker beyond traditional collagen metabolism.