To investigate whether liver-targeted Angptl4 suppression holds similar therapeutic potential as Angptl3 inhibition in lowering hyperlipidemia and atherosclerosis development, we compare ASO-mediated liver-targeted silencing of Angptl3 and Angptl4 alone and combined in APOE*3-Leiden.CETP mice, a well-established humanized mouse model for lipoprotein metabolism and cardiometabolic diseases. Here, APOE is linked to hyperlipidemia.