SLC22A5 encodes OCTN2 (organic cation transporter novel family member 2), a sodium-dependent membrane transporter essential for carnitine uptake across cell membranes 1. OCTN2 functions primarily in carnitine transport, a critical process for transferring long-chain fatty acids across the inner mitochondrial membrane for β-oxidation 1. The transporter localizes to the plasma membrane, including apical and brush border membranes, where it mediates high-affinity carnitine accumulation by cells and renal reabsorption 1. Loss-of-function mutations in SLC22A5 cause systemic primary carnitine deficiency (CTD), characterized by reduced intracellular carnitine accumulation, increased urinary carnitine loss, and low serum carnitine levels 1. This disorder presents clinically with hypoketotic hypoglycemia, hepatic encephalopathy, skeletal and cardiac myopathy, or sudden cardiac death, typically triggered by fasting or catabolic states 1. Among 358 subjects evaluated, 140 showed reduced carnitine transport, with SLC22A5 sequencing identifying causative variants in 84% of alleles 2. A major mechanism of disease involves impaired plasma membrane localization of OCTN2 protein, accounting for approximately 62% of loss-of-function variants 3. Oral carnitine supplementation at pharmacological doses effectively treats primary carnitine deficiency 1, and carnitine therapy mitigates hypoxia and chr5 kidney disease progression by maintaining carnitine homeostasis 4.