ABCA7: a potential mediator between cholesterol homeostasis and the host defense system

ABCA7 is a molecule with high homology to ABCA1, an essential protein for the generation of HDL. However, although exogenously transfected ABCA7 supports the generation of HDL, endogenous ABCA7 does not mediate this reaction. ABCA7 is regulated by sterol regulatory element-binding protein 2 whereby ABCA7 expression responds inversely to cellular sterol levels of ABCA1, indicating it has functions other than the elimination of cellular cholesterol. In fact, ABCA7 is strongly associated with phagocytosis of various targets, including microorganisms and apoptotic cells. Accordingly, helical apolipoproteins and statins enhance phagocytic activity through increasing ABCA7, by stabilizing it and by activating sterol regulatory element-binding protein 2. Recent genome-wide association studies identified single nucleotide polymorphisms of ABCA7 as risk factors of Alzheimer’s disease and schizophrenia. While physiological roles of ABCA7 are not completely understood and the grounds for the genome-wide association studies findings are also unknown, ABCA7 has become a focus of keen interest.