ANGPTL8 is a hepatic-derived hormone that functions as a physiological inhibitor of lipoprotein lipase (LPL), regulating serum triglyceride levels and lipid metabolism 1. The protein regulates fatty acid partitioning during fasting-refeeding transitions, directing triglycerides to adipose tissue storage in the fed state and forming complexes with ANGPTL3 and ANGPTL4 to coordinate LPL activity 12. Beyond lipid metabolism, ANGPTL8 plays complex roles in glucose homeostasis; while some evidence suggests improved insulin sensitivity and reduced hepatic glucose production, other studies indicate potential exacerbation of glucose metabolism disorders 32. ANGPTL8 is significantly elevated in type 2 diabetes, obesity, and metabolic syndrome, serving as a biomarker for these conditions 3. Emerging evidence reveals ANGPTL8 mediates macrophage recruitment via LILRB2/PirB signaling, contributing to nonalcoholic steatohepatitis (NASH) pathogenesis, with hepatocyte-specific ANGPTL8 knockout reducing liver inflammation and fibrosis 4. ANGPTL8 also associates with various cardiovascular pathologies including atherosclerosis, hypertension, and cardiomyopathy 2. These multifaceted roles position ANGPTL8 as a potential therapeutic target for cardiometabolic disorders, though its complex biology—with both beneficial and detrimental effects depending on context—requires further clarification 32.