ANGPTL4

ANGPTL4 (angiopoietin-like 4) is a secreted glycoprotein that functions as a central regulator of lipid metabolism through inhibition of lipoprotein lipase (LPL), thereby controlling triglyceride hydrolysis and fatty acid partitioning among tissues^[1][2]. Mechanistically, ANGPTL4 is induced by fasting, fatty acids, hypoxia, and peroxisome proliferator-activated receptor (PPAR) signaling, linking metabolic adaptation to nutrient availability and cellular stress responses^[1][3]. Proteolytic processing generates distinct N-terminal and C-terminal fragments with divergent biological activities; the N-terminal domain primarily mediates LPL inhibition, whereas the C-terminal fragment regulates angiogenesis, vascular permeability, cell adhesion, and tissue remodeling^[1][4]. In disease models, ANGPTL4 contributes to metabolic disorders, cardiovascular disease, inflammation, and cancer progression through regulation of lipid flux, endothelial barrier integrity, and cellular migration pathways^[1][3][5]. ANGPTL4 also modulates inflammatory responses and vascular leakage during pulmonary injury, highlighting its role in tissue-specific stress adaptation and disease pathogenesis^[5][4]. Compared with related angiopoietin-like family members, ANGPTL4 is distinguished by its strong responsiveness to fasting and lipid-derived signals and by the functional separation of its N-terminal lipid-regulatory and C-terminal non-metabolic activities^[1][4][5]. For experimental applications, neutralizing antibodies targeting ANGPTL4 have been used to investigate triglyceride metabolism and inflammatory injury models, supporting its value as a mechanistic target in metabolic and vascular research^[5][6].