Slc22a5, also known as organic cation transporter novel family member 2 (OCTN2), is a crucial gene encoding a transporter essential for carnitine uptake. Carnitine is vital for the β -oxidation of fatty acids, which involves transporting acyl moieties to mitochondria via the carnitine shuttle [1,3,5,6]. This process is integral to cell metabolism, providing an alternative energy source to glucose, especially in cancer cells where its expression can impact growth and proliferation [1].

In a study with the long-chain acyl-CoA dehydrogenase (LCAD) KO mouse, introducing one defective Slc22a5 allele (jvs) decreased free carnitine levels in the liver, kidney, and heart. However, major phenotypes of the LCAD KO mouse such as cardiac hypertrophy, fasting-induced hypoglycemia, and increased liver weight were not affected, suggesting that secondary carnitine deficiency may not play a major role in the pathophysiology of these phenotypes [4]. In macrophages, conditional knockout (CKO) of SIRPA transcriptionally downregulates Slc22a5, and targeting Slc22a5 renders mitophagy inhibition of macrophages in response to LPS stimuli, improving survival and deterring the development of septic acute kidney injury [2].

In conclusion, Slc22a5 is essential for maintaining carnitine homeostasis, which is crucial for fatty acid oxidation and cell metabolism. Model-based research, especially the use of KO and CKO mouse models, has provided insights into its role in various biological processes and disease conditions such as septic acute kidney injury and the pathophysiology related to fatty acid oxidation disorders [2,4].