NDRG1 as a sensor and mediator of endothelial stress: from homeostasis to inflammation and cardiovascular disease.

N-myc downstream-regulated gene 1 (NDRG1) is a multifunctional, stress-responsive protein with pleiotropic roles across diverse cell types. Although extensively studied in cancer, recent evidence points to its emerging, context-dependent functions in vascular endothelial cells. In this mini-review, we synthesize current knowledge on the regulation of NDRG1 under environmental stressors, such as hypoxia, inflammation, disturbed shear stress and heavy metal (iron, nickel, copper and cobalt) and its impact on endothelial homeostasis. We highlight NDRG1’s involvement in key processes including vascular inflammation, thrombosis, permeability and remodeling. Drawing parallels with its dualistic role in tumor biology, we propose that NDRG1 acts as a dynamic integrator of environmental cues in the endothelium, orchestrating adaptive or maladaptive responses depending on microenvironmental context. These insights support a broader conceptual framework positioning NDRG1 as a potential biomarker and therapeutic target in cardiovascular disease.