ATP-binding cassette transporter (ABC) A7 is an ABC family protein that is a so-called full-size ABC transporter, highly homologous to ABCA1, which mediates the biogenesis of high-density lipoprotein (HDL) with cellular lipid and helical apolipoproteins. ABCA7 mediates the formation of HDL when exogenously transfected and expressed; however, endogenous ABCA7 was shown to have no significant impact on the generation of HDL and was found to be associated with phagocytosis regulated by sterol regulatory element binding protein 2. Since phagocytosis is one of the fundamental functions of animal cells as an important responsive reaction to infection, injury and apoptosis, ABCA7 seems to be one of the key molecules linking sterol homeostasis and the host defense system. In this context, HDL apolipoproteins were shown to enhance phagocytosis by stabilizing ABCA7 against calpain-mediated degradation and increasing its activity, shedding light on a new aspect of the regulation of the host-defense system.
Roles of ATP-Binding Cassette Transporter (ABC) A7 in cholesterol homeostasisHigh-density lipoprotein (HDL) apolipoproteins, such as apolipoprotein (apo) A-and apoA-, are helical amphiphilic proteins bound to the HDL lipid surface in equilibrium with an aqueous phase. These helical apolipoproteins interact with the cell surface in their free form and generate HDL particles by removing cellular phospholipid and cholesterol [1][2][3] . Fibroblasts from patients with Tangier disease, a genetic HDL deficiency, lack the interaction with apolipoprotein 4, 5) due to mutations in ABCA1 [6][7][8] , indicating that this reaction is the main source of plasma HDL. The reaction is one of the major pathways of cellular cholesterol release along with diffusion-mediated nonspecific efflux 9) . Thus, ABCA1 is a key membrane protein for cholesterol homeostasis, for the generation of HDL and the release of cell cholesterol for its catabolism 10) . ABCA1 is one of the ABC family proteins consisting of two sets of multiple membranespanning domains plus the Walker motifs for ATP interaction 11, 12) , and is thereby classified as a so-called full-size ABC transporter.Human ABCA7 is another full-size ABC transporter showing the highest homology among those known to human ABCA1 (54%) and human ABCA4 (49%) 13) . On the other hand, its interspecies identity of the protein sequences is 79% between humans and mice, less than that of ABCA1 (95%) and ABCA4 (88%) 14)