Chow-fed mice lacking Abcg1 showed accumulation of phospholipids and neutral lipids, including cholesterol and triglyceride, in liver and lung. Mice lacking Abcg1 and Abcg4 showed high levels of oxysterols and ketosterols in the brain, which are toxic to neurons. These studies suggest that ABCG1 plays an important role in the removal of excess cholesterol from peripheral cells and that ABCG1 and ABCG4 protect cells from toxic sterols in the central nervous system. In addition to cholesterol removal from cells, ABCG1 has other physiological functions. The absence of Abcg1 in mice abolished the regulation of T-cell proliferation by liver X receptor signaling, suggesting that ABCG1 suppresses the proliferation of T cells. Expression of ABCG1 induced the apoptosis of cultured cells, but inhibited the apoptosis of macrophages by Remdesivir decreasing raft-dependent signaling of TLR4 and NOX2, and blocked apoptosis in prostate cancer cells by downregulating Akt signaling in raft domains. Abcg4 suppresses the proliferation of megakaryocyte progenitor cells by decreasing c-MPL signaling in raft domains. These findings suggest that ABCG1 and ABCG4 are involved in cell proliferation, apoptosis, and the immune response, and that these various functions may be related to the regulation of raft domains where many signaling pathways are executed. However, it is not clear if ABCG1 and ABCG4 are involved in the regulation of raft domains. Besides ABCG1 and ABCG4, ABCA1 is also involved in cholesterol efflux from cells. ABCA1 is a member of the A subfamily of ABC proteins, which has two TMDs and two NBDs. Mutations in ABCA1 cause a genetic disease, Tangier disease, characterized by the loss of HDL from serum. ABCA1 is expressed ubiquitously and mediates the efflux of cholesterol and PC to apolipoprotein A-I, which forms preb-HDL. Previous studies have shown that ABCA1 and ABCG1 or ABCG4 coordinately remove excess cholesterol from cells. ABCA1 disrupts raft domains, as detected by a loss of caveolin localization to raft domains, which leads to reduced Akt phosphorylation in response to signaling by epidermal growth factor. ABCA1 and ABCG1 have been reported to increase the proportion of cholesterol accessible to cholesterol oxidase, suggesting that the levels of cholesterol in non-raft domains are increased by the disruption of raft domains. These findings also raise the possibility that ABCG1 regulates raft domain structures by redistributing lipid molecules. In the Chinese hamster ovary mutant cell line, LY-A, ceramide transfer is impaired by a missense mutation in CERT, which transfers ceramide from the endoplasmic reticulum, where it is synthesized, to the Golgi, where it is used to synthesize SM.