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The signature action of aldosterone in the regulation of electrolyte and fluid balance is well established. However, the role of aldosterone as an important contributor to morbidity and mortality in heart failure has gained a heightened interest in recent years, but the mechanisms of this action are not well understood. Aldosterone is the principal physiological ligand for the mineralocorticoid receptor (MR), a ligand-activated transcription factor, that also binds to the physiological glucocorticoid, cortisol. Both classes of hormones bind with similar affinity to the MR, but the molecular basis of selective and tissue-specific effects of MR ligands are not yet fully documented. The structural and functional determinants of MR function are described and their significance is discussed