HSD11B2 encodes an NAD+-dependent enzyme that catalyzes the conversion of active glucocorticoids—primarily cortisol—to their inactive metabolites, chiefly cortisone. By inactivating glucocorticoids, HSD11B2 protects mineralocorticoid receptors from excessive glucocorticoid occupancy and regulates glucocorticoid access to glucocorticoid receptors, thereby safeguarding fetal development and gonadal function. The enzyme also catalyzes oxidation of 11-beta-hydroxytestosterone to 11-ketotestosterone, a major bioactive androgen, and metabolizes oxysterols that regulate immune cell migration. HSD11B2 is highly expressed in kidney, colon, pancreas, and placenta. Loss-of-function mutations in HSD11B2 cause apparent mineralocorticoid excess (AME), a rare autosomal recessive disorder characterized by early-onset hypertension, hypokalemia, salt sensitivity, and suppressed renin and aldosterone 1. Without functional HSD11B2, cortisol accumulates in renal collecting ducts and acts as a potent mineralocorticoid, driving sodium retention 2. Recessive HSD11B2 mutations can also present with thrombotic microangiopathy 3. In the general population, HSD11B2 polymorphisms correlate with salt-sensitive blood pressure elevation 4. Carbenoxolone, an 11β-HSD inhibitor, represents a therapeutic approach for modulating enzyme activity in disease states.