ABCA2

ABCA2: A Transporter Protein with Vital Roles in Cholesterol Homeostasis and Beyond

Description

ABCA2 (ATP-binding cassette transporter A2) is a critical protein that plays a crucial role in the regulation of cholesterol metabolism. It belongs to the ABC superfamily of transmembrane proteins that utilize ATP hydrolysis to transport various molecules across biological membranes. ABCA2 is primarily localized to the plasma membrane of cells involved in cholesterol efflux, such as macrophages and enterocytes.

Associated Diseases

Dysregulation of ABCA2 function has been implicated in a range of diseases, including:

• Tangier Disease: A rare genetic disorder characterized by an absence of functional ABCA2. It leads to impaired cholesterol efflux, accumulation of cholesterol in macrophages, and severe cardiovascular complications.
• Coronary Artery Disease (CAD): Studies have linked ABCA2 polymorphisms or mutations to an increased risk of CAD, suggesting a role for ABCA2 in the development of atherosclerosis.
• Neurodegenerative Disorders: Impaired cholesterol efflux via ABCA2 has been associated with neuroinflammatory processes and increased risk of Alzheimer‘s disease and Parkinson‘s disease.

Cholesterol Metabolism and Beyond

ABCA2 plays a central role in reverse cholesterol transport (RCT), the process by which excess cholesterol is removed from peripheral tissues and returned to the liver for excretion. It mediates the transfer of cholesterol from cells to extracellular lipid-poor apolipoprotein A-I (apoA-I) molecules, initiating the formation of cholesterol-rich high-density lipoproteins (HDLs). These HDLs are then transported to the liver via the scavenger receptor class B type I (SR-BI) and ultimately excreted.

Beyond its role in cholesterol metabolism, ABCA2 has also been implicated in other cellular processes, including:

• Immune Response: ABCA2 is involved in the regulation of immune cell function, particularly in macrophages.
• Retinal Function: ABCA2 contributes to the visual cycle by mediating the transport of all-trans-retinal from photoreceptor cells to retinal pigment epithelial cells.
• Placenta: ABCA2 facilitates the transfer of cholesterol and phospholipids from the mother to the developing fetus.

Did you Know ?

According to a recent study, carriers of a common ABCA2 gene variant (rs1800977) have been found to have a 20% lower risk of developing coronary artery disease compared to non-carriers.