However, a series of concerns (there are few MR in liver, the highest site of expression of this enzyme; the enzyme was expressed in the proximal tubule whereas MR are in the distal nephron; no mutations in the encoding gene were found in AME patients; the enzyme is bi-directional in homogenates yet apparently a unidirectional dehydrogenase in kidney in vivo) undermined the ‘one enzyme’ hypothesis. The gene discussed is NR3C2; the disease is apparent mineralocorticoid excess.