Importantly, although liver and intestine ABCA1 may be the most critical for lipidating newly synthesized lipid-free apoA-I, substantial additional cholesterol efflux to HDL occurs from other tissues. Studies in mice of “peripheral” cholesterol efflux suggest that 90 mg· d 1· kg 1 body weight of cholesterol is effluxed from peripheral tissues. 16 However, the tissues that contribute to the greatest extent to the mass of cholesterol in HDL are unknown, and the pathways by which they efflux cholesterol, whether by ABCA1 and/or other pathways, such as the ATP binding cassette transporter G1 (ABCG1) or the scavenger receptor class B type I (SR-BI)(see following sections), remain unknown. For example, when expressed per unit of protein or organ mass, adipose tissue contains more cholesterol than do most other organs, including the liver, 17 and adipocytes in culture have the ability to efflux cholesterol to HDL acceptors. 18 Thus, an important quantitative source of HDL-C mass could be adipose tissue. Although peripheral nonmacrophage cholesterol efflux may not be directly relevant to atherosclerosis per se, it could be important in contributing to the overall pool of HDL-C mass and therefore to HDL-C levels, and thus, it may indirectly influence cardiovascular risk. More investigation regarding the quantitative contribution of peripheral tissues to HDL-C and the mechanisms of efflux by these tissues is required.