ATP-binding cassette transporter-2 (ABCA2) as a therapeutic target.

The ATP binding cassette transporter ABCA2 is primarily an endolysosomal membrane protein that demonstrates pleiotropic functionalities, coalescing around the maintenance of homeostasis of sterols, sphingolipids and cholesterol. It is most highly expressed in brain tissue and ABCA2 knockout mice express neurological defects consistent with aberrant myelination. Increased expression of the transporter has been linked with resistance to cancer drugs, particularly those possessing a steroid backbone and gene expression (in concert with other genes involved in cholesterol metabolism) was found to be regulated by sterols. Moreover, in macrophages ABCA2 is influenced by sterols and has a role in regulating cholesterol sequestration, potentially important in cardiovascular disease. Accumulating data indicate the critical importance of ABCA2 in mediating movement of sphingolipids within cellular compartments and these have been implicated in various aspects of cholesterol trafficking. Perhaps because the functions of ABCA2 are linked with membrane building blocks, there are reports linking it with human pathologies, including, cholesterolemias and cardiovascular disease, Alzheimer's and cancer. The present review addresses whether there is now sufficient information to consider ABCA2 as a plausible therapeutic target.