PGPEP1 encodes pyroglutamyl-peptidase I, an enzyme that removes 5-oxoproline (pyroglutamate) residues from the N-terminus of peptides and proteins 1. This enzymatic activity makes modified proteins more susceptible to degradation by other proteases, as demonstrated in studies of gluten peptide processing where pyroglutamate modification can render peptides resistant to proteolytic degradation 1. However, comprehensive functional genomics analysis found no evidence for PGPEP1 involvement in coeliac disease pathology despite its location in a disease susceptibility locus 1. The gene has been implicated in metabolic regulation, with knockdown studies in Drosophila showing significant effects on fat storage and triglyceride levels, suggesting a role in adiposity control 2. Additionally, PGPEP1 expression is developmentally regulated in the hypothalamus, with decreased expression observed during neonatal maternal deprivation in mice, indicating potential involvement in early feeding responses 3. Beyond protein function, circular RNA derived from PGPEP1 (circPGPEP1) has emerged as an oncogenic factor in multiple cancers including colorectal, renal cell, and gastric cancers, where it promotes cell proliferation, metastasis, and immune escape through microRNA sponging mechanisms 456.