Beyond conventional treatment: ASGR1 Leading the new era of hypercholesterolemia management

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with hypercholesterolemia being a major risk factor. Although various lipid-lowering therapies exist, many patients fail to achieve optimal cholesterol control, highlighting the need for novel therapeutic approaches. ASGR1 (asialoglycoprotein receptor 1), predominantly expressed on hepatocytes, has emerged as a key regulator of cholesterol metabolism and low-density lipoprotein (LDL) clearance. This receptor's ability to regulate lipid homeostasis positions it as a promising target for therapeutic intervention in hypercholesterolemia and related cardiovascular diseases. This review critically examines the biological functions and regulatory mechanisms of ASGR1 in cholesterol metabolism, with a focus on its potential as a therapeutic target for hypercholesterolemia and related cardiovascular diseases. By analyzing recent advances in ASGR1 research, this article explores its role in liver-specific pathways, the implications of ASGR1 variants in CVD risk, and the prospects for developing ASGR1-targeted therapies. This review aims to provide a foundation for future research and clinical applications in hypercholesterolemia management.