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Sortilins: new players in lipoprotein metabolism

Purpose of review Sortilins are sorting receptors that direct proteins through secretory and endocytic pathways of the cell. Previously, these receptors have been shown to play important roles in regulating protein transport in neurons and to control neuronal viability and death in many diseases of the nervous system. Recent data, including genome-wide association studies, now suggest equally important functions for sortilins in control of systemic lipoprotein metabolism and risk of cardiovascular disease. This review discusses the evidence implicating two members of this gene family, sortilin and SORLA, in cardiovascular processes. Recent findings SORLA is a multifunctional receptor expressed in macrophages and vascular smooth muscle cells. It may act proatherogenic by promoting intimal SMC migration and by regulating apolipoprotein A-V dependent activation of lipoprotein lipase to modulate systemic triglyceride levels. Sortilin, encoded by the cardiovascular risk locus 1p13.3, is a novel regulator of hepatic lipoprotein production. It interacts with apolipoprotein B-100 to control release of very low-density lipoproteins, thereby affecting plasma cholesterol concentrations. Summary Recent data shed light on the importance of sorting receptors in control of cellular and systemic lipoprotein metabolism and how altered trafficking pathways may represent a major risk factor for dyslipidemia and atherosclerosis in the human population.