The article explores the role of very low-density lipoprotein (VLDL) in atherosclerotic cardiovascular disease (ASCVD) and its potential as a therapeutic target. VLDL, the precursor to low-density lipoprotein (LDL), plays a crucial role in lipid metabolism and is linked to increased cardiovascular risk. The article discusses the biogenesis, intracellular trafficking, and metabolism of VLDL, highlighting the importance of targeting VLDL in lipid-lowering strategies. Key enzymes and proteins involved in VLDL metabolism, such as lipoprotein lipase (LPL), hepatic lipase, and endothelial lipase, are reviewed, along with their regulatory factors. The article also examines current therapies for reducing LDL-C and triglyceride levels, including statins, PCSK9 inhibitors, and drugs targeting APOB, MTP, and ANGPTL3. The potential of VLDL-specific interventions, such as inhibiting VLDL secretion and metabolism, is explored, with a focus on the therapeutic benefits and challenges. The review concludes by emphasizing the need for further research to develop effective and safe methods for targeting VLDL in the management of ASCVD.The article explores the role of very low-density lipoprotein (VLDL) in atherosclerotic cardiovascular disease (ASCVD) and its potential as a therapeutic target. VLDL, the precursor to low-density lipoprotein (LDL), plays a crucial role in lipid metabolism and is linked to increased cardiovascular risk. The article discusses the biogenesis, intracellular trafficking, and metabolism of VLDL, highlighting the importance of targeting VLDL in lipid-lowering strategies. Key enzymes and proteins involved in VLDL metabolism, such as lipoprotein lipase (LPL), hepatic lipase, and endothelial lipase, are reviewed, along with their regulatory factors. The article also examines current therapies for reducing LDL-C and triglyceride levels, including statins, PCSK9 inhibitors, and drugs targeting APOB, MTP, and ANGPTL3. The potential of VLDL-specific interventions, such as inhibiting VLDL secretion and metabolism, is explored, with a focus on the therapeutic benefits and challenges. The review concludes by emphasizing the need for further research to develop effective and safe methods for targeting VLDL in the management of ASCVD.