Mitochondrial ornithine transporter 1 (SLC25A15)

Mitochondrial ornithine transporter 1 (SLC25A15) is a mitochondrial inner membrane transporter that exchanges cytosolic ornithine with mitochondrial citrulline and protons, serving a critical role in the urea cycle by enabling the detoxification of ammonia in hepatocytes. Loss-of-function mutations in SLC25A15 cause hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, a rare autosomal recessive disorder characterized by elevated blood ornithine and ammonia, with neurological dysfunction, protein intolerance, and risk of life-threatening hyperammonemic crises. SLC25A15 is a member of the solute carrier family 25, a large group of mitochondrial transporters, and is essential for linking the cytosolic steps of the urea cycle with intramitochondrial reactions. Treatment primarily involves ammonia-scavenging drugs, dietary protein restriction, and arginine supplementation, but direct pharmacological inhibitors or activators of SLC25A15 are not in clinical use. Deficiency of this transporter leads to accumulation of toxic ammonia, particularly affecting the central nervous system, and can result in severe clinical outcomes if untreated.

Other names

ORNT1ORC1Ornithine transporter 1Ornithine carrier 1Solute carrier family 25 member 15Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome proteinD13S327HHH proteinSolute carrier family 25 (mitochondrial carrier; ornithine transporter) member 15

Drugs do not directly inhibit SLC25A15 but act by scavenging ammonia or supporting the deficient pathway