• A recent study reveals that ezetimibe monotherapy increases serum coproporphyrin I (CPI) concentrations in healthy individuals, potentially affecting OATP1B1 function. • Co-administration of ezetimibe and rifampin further elevates CPI levels, complicating the assessment of drug interactions in patients undergoing combination therapies. • The research supports CPI as a reliable biomarker for monitoring OATP1B1 activity, crucial for personalized medicine approaches and reducing adverse drug reactions. • Ezetimibe-glucuronide, a metabolite of ezetimibe, significantly reduces cellular CPI accumulation, suggesting a broader role in modulating transporter function beyond cholesterol reduction.