LIPID METABOLISM: Edited by Henry GinsbergRegulation of lipoprotein lipase-mediated lipolysis of triglyceridesBasu, Debapriya; Goldberg, Ira J.Author Information Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA Correspondence to Debapriya Basu, PhD, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New Science Building 623B, 435 East 30th Street, New York, NY 10016, USA. Tel: +1 646 501 0586; e-mail: [email protected] Current Opinion in Lipidology: June 2020 - Volume 31 - Issue 3 - p 154-160 doi: 10.1097/MOL.0000000000000676 Buy Metrics Abstract Purpose of review To discuss the recent developments in structure, function and physiology of lipoprotein lipase (LpL) and the regulators of LpL, which are being targeted for therapy. Recent findings Recent studies have revealed the long elusive crystal structure of LpL and its interaction with glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1). New light has been shed on LpL being active as a monomer, which brings into questions previous thinking that LpL inhibitors like angiopoietin-like 4 (ANGPTL4) and stabilizers like LMF1 work on disrupting or maintaining LpL in dimer form. There is increasing pharmaceutical interest in developing targets to block LpL inhibitors like ANGPTL3. Other approaches to reducing circulating triglyceride levels have been using an apoC2 mimetic and reducing apoC3. Summary Lipolysis of triglyceride-rich lipoproteins by LpL is a central event in lipid metabolism, releasing fatty acids for uptake by tissues and generating low-density lipoprotein and expanding high-density lipoprotein. Recent mechanistic insights into the structure and function of LpL have added to our understanding of triglyceride metabolism. This has also led to heightened interest in targeting its posttranslational regulators, which can be the next generation of lipid-lowering agents used to prevent hypertriglyceridemic pancreatitis and, hopefully, cardiovascular disease. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.