Human d-Glycerate Kinase, Encoded by GLYCTK and Deficient in d-Glyceric Aciduria, Is a Mitochondrial Enzyme

d-glyceric aciduria is a very rare inborn error of serine and fructose metabolism which is caused by d-glycerate kinase (GLYCTK) deficiency. So far, 18 individuals with this tentative diagnosis have been reported. Patients present with a wide range of clinical phenotypes, but asymptomatic cases have also been described. Given the highly variable clinical outcomes it has been suggested that d-glycerate kinase deficiency may be a mere biochemical variant rather than a disease. Previously, it was proposed and widely distributed in public databases, that two GLYCTK isoforms, which result from alternative splicing, are ubiquitously expressed in human tissues. It was further stated that the two isoforms are differentially localized in the cytosol and in mitochondria. Here, we show that human GLYCTK exclusively localizes to mitochondria. We propose that mitochondrial GLYCTK represents the functional enzyme and that the second transcript variant is nonfunctional under physiological conditions.