NUPR1 is a stress-inducible transcription factor that converts cellular stress signals into adaptive gene expression programs, playing multifaceted roles in cell survival and disease progression. Functionally, NUPR1 regulates cell cycle progression, apoptosis, autophagy, and DNA repair responses 123. It protects cells from genotoxic stress through complex formation with TP53 and EP300, inducing CDKN1A expression to halt cell cycle progression 4. In pancreatic cancer, NUPR1 promotes survival by activating RELB-mediated transcription 5, while in cardiac tissue it inhibits autophagy-induced apoptosis via FOXO3 interaction 6. Recent studies reveal NUPR1's critical roles in treatment resistance and iron homeostasis. NUPR1 promotes ferroptosis resistance by upregulating lipocalin-2 (LCN2), reducing iron accumulation and oxidative damage 7. In hepatocellular carcinoma, NUPR1 confers radiation resistance by maintaining ROS homeostasis through AhR/CYP pathway inhibition 8, while in oral squamous cell carcinoma it promotes proliferation and metastasis via TFE3-dependent autophagy activation 9. Additionally, NUPR1 drives immunosuppression in tumor-associated macrophages through lactylation-mediated M2 polarization and PD-L1 upregulation, limiting anti-tumor immunity 10. In aged organisms, increased NUPR1-LCN2 axis activity suppresses stemness and tumorigenesis through iron insufficiency 11.