Slc25a1, also known as the mitochondrial citrate carrier (CIC), is a key metabolic switch. It belongs to a family of mitochondrial transporters and mediates the transport of citrate across the mitochondrial membrane, playing a role in pathways like fatty acid oxidation (FAO), fatty acid synthesis, glycolysis, and gluconeogenesis [1,3,5,6]. Genetic models such as knockout (KO) mice are valuable for studying its functions.

Global knockout of Slc25a1 in mice leads to various heart malformations, recapitulating congenital heart defects seen in 22q11.2 deletion syndrome. Trophoblast-specific Slc25a1 deletion also results in heart anomalies, suggesting its role in regulating placental development to ensure embryonic heart morphogenesis [2,5]. In pancreatic cancer, oncogenic KRASG12D upregulates Slc25a1 via GLI1, which rewires lipid metabolism. Pharmacologic inhibition of Slc25a1 suppresses pancreatic tumorigenesis in KrasG12D/+ mice on a high-fat diet [1]. In acute myeloid leukemia (AML), high levels of Slc25a1 are associated with unfavorable prognosis, and its inhibition can reduce AML cell proliferation and increase apoptosis [4].

In conclusion, Slc25a1 is crucial for metabolic regulation and normal development. Model-based research, especially KO mouse models, has revealed its significance in congenital heart diseases and cancer. Understanding Slc25a1 provides insights into disease mechanisms and potential therapeutic targets for these conditions.