Aldehyde reductase reduces a wide variety of toxic and physiological aldehydes with a marked preference for the negatively charged substrates such as glucuronate. Reduction of glucuronate to gulonate is a step in inositol catabolism, a process specific to the kidney cortex. Administration of aldehyde reductase inhibitor AL1576 to mice increases urinary output of glucuronate and decreases output of vitamin C. Aldehyde reductase mRNA with a 319 bp 5'-untranslated region is expressed ubiquitously in murine tissues. A new isoform with a short 64 bp 5'-untranslated region is found predominantly in kidney resulting in a 10-fold higher enzyme activity observed in this organ compared to other tissues. Moderate level of the new transcript is found in liver, intestine and stomach, while brain, heart, lung, spleen, ovary and testis have low to insignificant levels. The short transcript is absent during embryonic development and is first observed in the murine kidney on the 6-th postnatal day. The abundance of the short transcript and enzyme activity increases sigmoidally with age; the sharpest increase occurs during the third week of life. As shown by immunohistochemistry, aldehyde reductase expression is limited to the proximal tubules and parietal epithelium of the Bowman's capsule. In mouse, the intensity of staining in tubules increases with age suggesting that induction in aldehyde reductase expression is part of the renal tubular maturation. Human kidney also exhibits proximal tubular localization and the two mRNA transcripts of aldehyde reductase. Immunoreactive protein is present in the 9-week-old fetal kidney, indicating that the induction of aldehyde reductase in human occurs early in development.