SLC47A1 encodes multidrug and toxin extrusion protein 1 (MATE1), which functions as a H+/organic cation antiporter facilitating the efflux of endogenous metabolites, drugs, and toxins through kidney and liver into urine and bile 1. The protein plays a crucial role in metformin pharmacokinetics, with genetic variants affecting drug response in type 2 diabetes patients. Meta-analysis revealed that the SLC47A1 rs2289669 polymorphism is associated with improved glycemic response to metformin, with A allele carriers showing greater HbA1c reduction compared to GG genotype patients 2. However, individual studies have shown mixed results regarding the clinical significance of SLC47A1 variants on metformin efficacy and pharmacokinetics 34. Beyond drug transport, SLC47A1 has emerged as a critical regulator of cellular lipid metabolism and ferroptosis resistance. The protein acts as a lipid flippase that blocks ferroptosis by preventing ACSL4-SOAT1-mediated production of polyunsaturated fatty acid cholesterol esters, with expression regulated by PPARA 5. Epigenetic regulation through DNA methylation of a 5' CpG island contributes to interindividual variability in hepatic MATE1 expression, explaining pharmacokinetic differences not attributable to genetic variants alone 6.