APOA1

APOA1 is the gene that encodes apolipoprotein A-I, the principal protein component of high-density lipoprotein (HDL) particles. It is synthesized mainly by the liver and intestine and secreted into the bloodstream, where ApoA-I serves as the major structural scaffold of HDL and is essential for HDL particle formation and function.

ApoA-I consists of about 243 amino acids and forms amphipathic alpha-helices that stabilize lipid binding. In plasma, it interacts with the ABCA1 transporter on peripheral cells to promote cholesterol and phospholipid efflux, generating nascent discoidal HDL particles. Lecithin–cholesterol acyltransferase (LCAT) then esterifies cholesterol, maturing HDL into spherical particles enriched in cholesteryl esters.

The APOA1 gene is located on chromosome 11 in humans. Genetic variants can influence HDL cholesterol levels and cardiovascular risk. Mutations in APOA1 can cause familial hypoalphalipoproteinemia and, in some cases, hereditary apoA-I amyloidosis, in which amyloid deposits derived from ApoA-I accumulate in organs such as the kidney and heart. A well-known rare variant is ApoA-I Milano (R173C), associated with altered HDL composition and cardiovascular outcomes in research contexts.

Clinically, low ApoA-I or HDL cholesterol is associated with increased cardiovascular risk, while ApoA-I levels are used in research and, in some cases, clinical assessment of HDL function. ApoA-I remains a therapeutic target in strategies aiming to enhance reverse cholesterol transport.