The novel member of the ATP binding cassette (ABC) gene family of transporters, ABC1, encodes the cholesterol-efflux regulatory protein termed CERP. When expressed in a heterologous system such as the Xenopus oocyte, ABC1 behaves as an electroneutral anion exchanger with a characteristic pharmacological profile and cAMP-dependent regulation. A similar profile was determined in mouse macrophages and used to demonstrate a role for ABC1 protein in the secretion of leaderless proteins such as IL-1β, in mammals. Furthermore, it was shown that ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidyl-serine. Mutations in ABC1 cause Tangier disease, plasma familial HDL deficiency and premature atherosclerosis. Although the exact mechanism underlying these processes is not clearly resolved, ABC1 mutations are associated with defects in cellular cholesterol efflux. This is a major breakthrough in the field of molecular genetic analysis for coronary heart disease, with important implications for diagnosis, pharmacology as well as genotype-phenotype correlation. The molecular structure, transport properties and pharmacology as well as the role of ABC1-CERP in apoptosis and cholesterol transport will be discussed.
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