PEPD encodes a dipeptidase that hydrolyzes dipeptides with a prolyl or hydroxyprolyl residue at the C-terminus, with Gly-Pro as the preferred substrate. The enzyme plays an important role in collagen metabolism due to the high level of iminoacids in collagen. Beyond its classical intracellular enzymatic function, PEPD has recently emerged as a regulator of adipose tissue homeostasis and systemic metabolism 1. In obesity, PEPD expression decreases in adipose tissue while circulating levels increase; secreted PEPD promotes fibro-inflammation and insulin resistance through EGFR signaling in macrophages and adipocytes 1. A genome-wide association study identified PEPD among genes that uncouple excess adiposity from cardiometabolic complications, suggesting roles in insulin-glucose signaling and adipocyte function 2. At the population level, gnomAD v4.1 classifies PEPD as LoF-tolerant (LOEUF=1.13); this is distinct from clinical pathogenicity—the gene harbors 78 pathogenic or likely pathogenic ClinVar variants, and biallelic loss-of-function mutations cause prolidase deficiency, a rare autosomal recessive disorder characterized by skin lesions, respiratory infections, and immunological impairment 3. Recent evidence suggests that decreased PEPD activity before Parkinson's disease onset may contribute to early pathophysiological changes detectable in plasma 4.