Lipoprotein lipase transporter GPIHBP1 and triglyceride-rich lipoprotein metabolism

Increased plasma triglyceride serves as an independent risk factor for cardiovascular disease (CVD). Lipoprotein lipase (LPL), which hydrolyzes circulating triglyceride, plays a crucial role in normal lipid metabolism and energy balance. Hypertriglyceridemia is possibly caused by gene mutations resulting in LPL dysfunction. There are many factors that both positively and negatively interact with LPL thereby impacting TG lipolysis. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a newly identified factor, appears essential for transporting LPL to the luminal side of the blood vessel and offering a platform for TG hydrolysis. Numerous lines of evidence indicate that GPIHBP1 exerts distinct functions and plays diverse roles in human triglyceride-rich lipoprotein (TRL) metabolism. In this review, we discuss the GPIHBP1 gene, protein, its expression and function and subsequently focus on its regulation and provide critical evidence supporting its role in TRL metabolism. Underlying mechanisms of action are highlighted, additional studies discussed and potential therapeutic targets reviewed.