NRDC (nardilysin convertase) is a metalloendopeptidase that functions as a multifunctional regulator of cellular processes through both proteolytic and non-proteolytic mechanisms. Mechanistically, NRDC cleaves peptide substrates at dibasic arginine pairs and serves as a specific receptor for heparin-binding EGF-like growth factor, enhancing HB-EGF-dependent cell migration via erbB1 signaling 1. NRDC also regulates protein synthesis and protein degradation pathways; it activates polo-like kinase 3 (Plk3) through site-specific scission, promoting apoptosis and suppressing pancreatic cancer development 2. In hematopoietic stem cells, NRDC controls self-renewal capacity by regulating protein synthesis in response to replication stress 3. Exercise-responsive miR-136-3p targets NRDC to modulate glucose uptake and myogenesis, representing inter-organ communication between pancreatic islets and skeletal muscle 4. Disease relevance is substantial: NRDC expression exhibits context-dependent roles in cancer—suppressing pancreatic ductal adenocarcinoma and associated metastasis while promoting colorectal cancer through HDAC1/p53-dependent mechanisms 5. NRDC is consistently expressed in extramammary Paget's disease, with reduced expression in lesion margins correlating with tumor cell invasion 6. Additionally, NRDC functions as a mitochondria-related biomarker in ischemic stroke, with decreased NRDC levels associated with mitochondrial damage and oxidative stress 7.