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Scavenger receptor class B type I (SR-BI) plays a central role in high-density lipoprotein (HDL) metabolism. Its major role in cholesterol uptake and reverse cholesterol transport (RCT) has been confirmed in several mouse studies. The role of SR-BI in humans is unclear. A newly described missense mutation of SR-BI (P297S) was found in patients with elevated levels of HDL cholesterol. We aimed to investigate the influence of this mutation on the interaction between SR-BI and HDL.