SLC47A1 encodes a multidrug efflux pump that functions as a proton/organic cation antiporter, mediating the excretion of cationic compounds through the kidneys and liver into urine and bile. The transporter handles both endogenous metabolites—including creatinine, thiamine, agmatine, and estrone-3-sulfate—and xenobiotic substrates. SLC47A1 also transports polyamines such as putrescine and plays a likely role in regulating cationic compound transport across the blood-testis barrier. Recent evidence reveals an unexpected function for SLC47A1 in lipid homeostasis and ferroptosis regulation 1. The transporter acts as a lipid flippase that blocks ferroptosis sensitivity by preventing the accumulation of polyunsaturated fatty acid cholesterol esters; this activity is regulated by the transcription factor PPARA. Genetic loss-of-function studies in mice and analysis of human loss-of-function variants establish SLC47A1 as a causal gene for kidney disease 2. Clinically, SLC47A1 variants influence metformin pharmacokinetics and efficacy in type 2 diabetes. Meta-analysis of drug-naive patients shows that the SLC47A1 rs2289669 A allele is associated with greater reductions in hemoglobin A1c compared to the GG genotype 3, though individual studies report inconsistent effects 4. Pharmacological or genetic blockade of the PPARA-SLC47A1 pathway enhances ferroptosis-inducer efficacy in cancer models, suggesting potential therapeutic applications.