SLC22A5

SLC22A5 is a human gene that encodes the organic cation/carnitine transporter 2 (OCTN2), a member of the solute carrier 22 (SLC22) family. The gene is located on chromosome 5q31.1 and the encoded protein typically features multiple transmembrane domains, with the transporter functioning at the cell membrane to move carnitine and related substrates across the plasma membrane.

OCTN2 functions as a high-affinity, Na+-dependent transporter for carnitine. It plays a key role in dietary carnitine absorption in the intestine and in the reabsorption of filtered carnitine in the kidney, contributing to whole-body carnitine homeostasis. Through its activity, OCTN2 supports the carnitine shuttle required for the transport of long-chain fatty acids into mitochondria for beta-oxidation, which is essential for energy production, especially in tissues with high energy demands such as heart and skeletal muscle.

Mutations in SLC22A5 cause primary systemic carnitine deficiency (also referred to as primary carnitine deficiency or carnitine transporter deficiency). The disorder is inherited in an autosomal recessive manner and results from reduced or absent OCTN2 function. Biochemically, affected individuals have low plasma carnitine levels and increased urinary loss. Clinically, they may present in infancy or later with hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, muscle weakness, and, if untreated, potentially life-threatening events. Early diagnosis and treatment with oral L-carnitine can restore carnitine levels and markedly improve outcomes.

Diagnosis is based on biochemical testing showing low plasma carnitine and genetic testing identifying bi-allelic variants in SLC22A5. Management centers on lifelong L-carnitine supplementation, regular monitoring of carnitine status, and addressing any cardiac or metabolic complications.