VASCULAR BIOLOGY: Edited by M. Luisa Iruela-ArispeANGPTL4 a multifunctional protein involved in metabolism and vascular homeostasisFernández-Hernando, Carlos; Suárez, YajairaAuthor Information Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA Correspondence to Carlos Fernández-Hernando, PhD, Yale University School of Medicine, 10 Amistad Street, Amistad Research Building 337-B, New Haven, CT 06520, USA. Tel: +1 (203) 737 4615; fax: +1 (203) 737 2290; e-mail: email@example.com Current Opinion in Hematology: May 2020 - Volume 27 - Issue 3 - p 206-213 doi: 10.1097/MOH.0000000000000580 Buy Metrics Abstract Purpose of review Since the first discovery of Angiopoetin-like 4 (ANGPTL4) in 2000, the involvement of ANGPTL4 in different aspects of lipid metabolism and vascular biology has emerged as an important research field. In this review, we summarize the fundamental roles of ANGPTL4 in regulating metabolic and nonmetabolic functions and their implication in lipid metabolism and with several aspects of vascular function and dysfunction. Recent findings ANGPTL4 is a secreted glycoprotein with a physiological role in lipid metabolism and a predominant expression in adipose tissue and liver. ANGPTL4 inhibits the activity of lipoprotein lipase and thereby promotes an increase in circulating triglyceride levels. Therefore, ANGPTL4 has been highly scrutinized as a potential therapeutic target. Further involvement of ANGPTL4 has been shown to occur in tumorigenesis, angiogenesis, vascular permeability and stem cell regulation, which opens new opportunities of using ANGPTL4 as potential therapeutic targets for other pathophysiological conditions. Summary Further determination of ANGPTL4 regulatory circuits and defining specific molecular events that mediate its biological effects remain key to future ANGPTL4-based therapeutic applications in different disease settings. Many new and unanticipated roles of ANGPTL4 in the control of cell-specific functions will assist clinicians and researchers in developing potential therapeutic applications. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.