Abstract: The ATP-binding cassette (ABC) superfamily of genes encodes membrane proteins that transport many kinds of substrates across membranes. Based on amino acid sequence similarities and phylogeny, 48 ABC genes in the human genome were divided into seven subfamilies: ABCA-ABCG. Among those subfamilies, ABCA transporters have a unique topology and members of it had expanded twice by gene duplication after the divergences between amphibian and mammal respectively. The new duplicated genes are well retained in rodent and carnivore while half of them have become pseudogenes or been lost in primate genome. Transporters of the ABCA subclass serve critical physiological functions in the transmembrane transport of endogenous lipid and cholesterol substrates and mutations of some of them cause human genetic diseases.