Activating and inactivating mutations of the human mineralocorticoid receptor

&NA; Numerous lines of evidence indicate that long‐term control of blood pressure is ultimately determined by the kidney via adjustment of net sodium balance. Fine regulation of renal sodium reabsorption takes place in the distal nephron under the control of the renin‐angiotensin‐aldosterone system and its principal effector molecule in the kidney, the mineralocorticoid receptor. Insights into the physiology of this system have been gained in recent years via the study of human diseases caused by both gain‐of‐function and loss‐of‐function mutations in this receptor. We review the mechanisms by which these mutations affect blood pressure and the implications these findings have for improved understanding of cardiovascular physiology and mineralocorticoid biology. Curr Opin Endocrinol Diabetes 10:186–190 © 2003 Lippincott Williams & Wilkins.