APOC

ApoC, or apolipoprotein C, denotes a small family of exchangeable apolipoproteins that associate with triglyceride-rich lipoproteins such as chylomicrons and VLDL. The APOC gene family comprises APOC1, APOC2, APOC3 and APOC4; these genes are clustered on chromosome 19 in humans, near the APOE gene. The encoded proteins are small secreted apolipoproteins produced mainly by the liver and intestine and circulate bound to lipoproteins, where they exchange rapidly between particles.

ApoC-I is a very small protein (roughly 6–7 kDa) enriched in HDL that modulates lipoprotein interactions and lipid transfer; it can influence cholesteryl ester transfer protein activity and receptor binding. ApoC-II is an essential activator of lipoprotein lipase, enabling hydrolysis of triglycerides on chylomicrons and VLDL; defects in ApoC-II function or expression can cause severe hypertriglyceridemia. ApoC-III acts as a regulator that inhibits lipoprotein lipase and delays hepatic uptake of triglyceride-rich particles, promoting higher plasma triglyceride levels. In humans, loss-of-function mutations in APOC3 are associated with lower triglycerides and reduced cardiovascular risk, and antisense therapies targeting APOC3 have been explored clinically. ApoC-IV is the least characterized member; it is expressed at low levels in the liver and its precise role in lipoprotein metabolism remains under study.

Role in disease and therapy: Variation in ApoC levels influences risk for hypertriglyceridemia and pancreatitis; ApoC3 inhibitors have been investigated as treatments for severe triglyceride disorders. The ApoC proteins function as exchangeable components of lipoproteins, helping coordinate lipid delivery and lipoprotein remodeling.