NDRG2 is a member of the N-myc downstream-regulated gene family predominantly expressed in astrocytes throughout the brain 1. Its primary function involves regulating cell proliferation and differentiation 2, with emerging roles in neuroprotection and immune regulation. Mechanistically, NDRG2 operates through multiple signaling pathways. It regulates the Wnt/β-catenin pathway by down-regulating CTNNB1-mediated transcriptional activation [UniProt]. In astrocytes, NDRG2 modulates NF-κB/complement C3 signaling to regulate synaptic plasticity 3. The protein also binds PPM1A to restrict dephosphorylation of Smad2/3, controlling MMP-9 production and blood-brain barrier integrity 4. NDRG2 expression is regulated by glucocorticoids and antidepressants 56. NDRG2 functions as a tumor suppressor in diverse cancers including glioma and mesothelioma, where downregulation associates with disease progression 78. In neurological disease, NDRG2 dysfunction contributes to stroke, neurodegeneration (Alzheimer's and Parkinson's disease), depression, and cognitive dysfunction in diabetes 13. Clinical relevance includes potential biomarker utility; exercise-induced NDRG2 upregulation in diabetic patients correlated with cognitive improvement 3. Upregulating NDRG2 represents a promising therapeutic strategy for malignancies and neuroprotection 7.