NDRG1 (N-myc downstream regulated 1) is a stress-responsive protein with multifaceted roles in cellular homeostasis and disease prevention. Functionally, NDRG1 acts as a metastasis suppressor and regulates critical cellular processes including cell differentiation, proliferation, and stress responses 1. Mechanistically, NDRG1 operates through multiple signaling axes: it interacts with orphan nuclear receptor Nur77 to inhibit NF-κB transcriptional activity in endothelial cells 2, suppresses CDC42-mediated filopodia formation to reduce cancer invasiveness 3, and promotes Stat1 ubiquitination to enhance drug sensitivity in colorectal cancer 4. Additionally, NDRG1 participates in the PIM1/P-NDRG1(S330)/PTBP1 axis regulating endothelial-to-mesenchymal transition 5, and its mRNA stability is regulated by NSUN6-mediated m5C methylation, affecting DNA repair and radioresistance 6. Disease relevance spans vascular pathology, cancer progression, and neurological disorders. NDRG1 knockdown attenuates atherosclerosis progression and reduces endothelial inflammation 2, while NDRG1 upregulation predicts therapeutic response to KDM1A inhibitors in gastric cancer 7. NDRG1 mutations cause Charcot-Marie-Tooth disease type 4D, reflecting its essential role in peripheral nerve myelination. Clinically, NDRG1 downregulation in tumors correlates with poor prognosis, and NDRG1 serves as a predictive biomarker for chemotherapy and targeted therapy responses, suggesting therapeutic potential through NDRG1-modulating agents.