NR3C2 encodes the mineralocorticoid receptor (MR), a ligand-dependent nuclear transcription factor that binds aldosterone and corticosterone to regulate ion and water transport, blood pressure, and potassium levels 1. As a member of the nuclear receptor 3 group C family, NR3C2 functions as a sequence-specific DNA-binding transcription factor that transactivates mineralocorticoid response elements in target genes 1. Beyond classical endocrine functions, NR3C2 contributes to cognitive performance through genetic variation affecting verbal memory 2, and plays roles in folliculogenesis, fat metabolism, and insulin resistance 3. Clinically, NR3C2 mutations cause pseudohypoaldosteronism type 1 (PHA1), characterized by mineralocorticoid resistance presenting as salt wasting, hyperkalemia, and elevated plasma renin and aldosterone 4. NR3C2 variants are associated with early-onset hypertension with severe pregnancy exacerbation 4. Emerging evidence links NR3C2 to broader disease susceptibility: loss-of-function mutations disrupt sleep and social behavior relevant to autism spectrum disorder 5, and NR3C2 variants confer risk for polycystic ovary syndrome 3. In acute lymphoblastic leukemia, NR3C2 mutations drive chemotherapy resistance and relapse 6. MR overactivation contributes to pathology across multiple organ systems, making MR antagonists therapeutically important in heart failure, diabetic kidney disease, and hypertension 7.