ANGPTL4 is a secreted protein that functions primarily as a lipoprotein lipase (LPL) inhibitor, regulating triglyceride clearance and lipid metabolism 1. The cleaved form of ANGPTL4 demonstrates higher LPL inhibitory activity than uncleaved protein, suppressing fatty acid release from triglyceride-rich lipoproteins including VLDLs and chylomicrons 2. This function affects tissue-specific fatty acid uptake and distribution, making ANGPTL4 central to lipid homeostasis. Beyond lipid metabolism, ANGPTL4 exhibits pleiotropic effects across multiple tissues. In diabetic kidney disease, podocyte- and tubule-derived ANGPTL4 promotes fibrogenesis through Integrin β1 interaction, driving epithelial-to-mesenchymal transition and pro-inflammatory responses 3. In diabetic cardiomyopathy, ANGPTL4 is transcriptionally activated by FOXO1 to promote cardiomyocyte senescence, which SGLT2 inhibitors ameliorate by suppressing this pathway 4. In cancer contexts, ANGPTL4 secretion by activated hepatic stellate cells and endothelial cells promotes colorectal cancer liver metastasis and gastric cancer progression via the ANGPTL4-SDC4 axis 56. Clinically, liver-targeted ANGPTL4 silencing by antisense oligonucleotides reduces plasma triglycerides and atherosclerotic lesion development without systemic adverse effects 7, suggesting therapeutic potential for metabolic and cardiovascular diseases while avoiding complications of systemic ANGPTL4 inhibition.