The abnormality of reverse cholesterol transport (RCT) induces the disorder of lipid metabolism, which is a key factor in the pathogenesis of atherosclerosis. It is important to explore the roles and regulatory mechanisms of key proteins mediated RCT in lipid metabolism. These are also important significance to elucidate the molecular mechanism of atherosclerosis. In this topic collection papers, we discuss the effects of liraglutide, momordicin and growth differentiation factor 11 on cholesterol efflux and the expressions of key proteins ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor class B type Ⅰ in RCT. From different angles, we explain the molecular mechanism of RCT key proteins involved in the regulation of cholesterol efflux by drugs or small molecules.