Identification of a Gain-of-Function <i>LIPC</i> Variant as a Novel Cause of Familial Combined Hypocholesterolemia

Abstract

We identified and characterized a novel rare variant in the <i>LIPC</i> gene in a family who presents with dominant familial combined hypocholesterolemia. This gain-of-function variant makes <i>LIPC</i> the second identified gene, after <i>ANGPTL3</i>, causally involved in familial combined hypocholesterolemia. Our mechanistic data highlight the critical role of hepatic lipase phospholipase activity in LDL cholesterol homeostasis and suggest a new LDL clearance mechanism.