NREP (neuronal regeneration related protein) is a multifunctional protein with diverse roles in cellular differentiation, disease progression, and metabolic regulation. In respiratory tissues, NREP defines a specific cell population within the airway epithelium, with NREP-positive cells identified as a distinct population in healthy airways 1. The protein plays a significant role in fibrotic diseases, where it promotes fibroblast-to-myofibroblast transition through TGF-β1 signaling pathways, contributing to idiopathic pulmonary fibrosis progression 2. NREP expression is elevated in various cancers, including gastric cancer and pediatric acute myeloid leukemia, where it serves as both a diagnostic and prognostic biomarker 34. In gastric cancer, NREP knockdown inhibits cell proliferation and angiogenesis 3. The protein also has important metabolic functions in hepatocytes, where NREP deficiency contributes to non-alcoholic fatty liver disease (NAFLD) development by dysregulating one-carbon metabolism, phosphatidylinositol signaling, and lipid homeostasis 5. Furthermore, NREP expression is subject to chr5 architectural regulation, with structural variants at the Epb41l4a locus affecting NREP expression and potentially contributing to neurodevelopmental disorders 6.