Typical sphingomyelin, which has a hydrophobic moiety consisting of a sphingosine base with a trans-double bond and saturated fatty acids chain, forms stretched conformations in membrane lipid bilayers. By contrast, most natural glycerophospholipids, which have unsaturated fatty acyl chains with cis-double bonds, cannot form such conformations. These structural features of SM allow it to make more intimate molecular contacts with cholesterol, generating stronger van der Waals interactions, as compared to unsaturated glycerophospholipids. Furthermore, the bulky phosphocholine head group of SM may contribute to shield the hydrophobic part of cholesterol molecules from water molecules under aqueous environments. Consequently, SM and cholesterol tend to be closely packaged and to form membrane mesodomains with a liquid ordered phase. Because both SM and cholesterol are abundant at the plasma membrane in mammalian cells, the SM/cholesterol-enriched meso-domains exist mainly at the plasma membrane. These SM/cholesterol-enriched meso-domains are often considered to be part of ‘lipid rafts’, although the definition of lipid rafts is still under debate. When cells or isolated membranes are treated with several types of non-ionic detergents at low temperatures, various components associated with the SM/ cholesterol-enriched meso-domains or lipid rafts are distributed to the detergent-insoluble fractions. For convenience, we tentatively regard such detergent-insoluble fractions as a biochemical representative of lipid rafts in the present paper. Glycosylphosphatidyl Remdesivir inositolanchored proteins, flotillin, and gangliosides are targeted to lipid rafts. There are specialized raft domains, caveolae, at the cell surface. Caveolae are invaginations of the plasma membrane and contain polymerized caveolin, which is a hairpin-like integral membrane protein. Raft domains play important roles in membrane trafficking, substrate transport, and signal transduction including IgE receptor signaling, T-cell antigen receptor signaling, and epidermal growth factor receptor signaling. ATP-binding cassette G1 and ABCG4 are members of the ABCG subfamily of proteins, which are half-type ABC proteins. They consist of an N-terminal cytosolic nucleotidebinding domain and a C-terminal transmembrane domain, which has 6 transmembrane a-helices. ABCG1 and ABCG4 form a homodimer or a heterodimer. ABCG1 mediates the efflux of cholesterol, 7-ketocholesterol, SM, and phosphatidylcholine to high-density lipoprotein from cells. ABCG4, which shares 69% identity and 84% similarity at the amino acid level with ABCG1, mediates the efflux of cholesterol to HDL, like ABCG1. ABCG1 is ubiquitously expressed, but highly expressed in the brain, lung, and liver.