Purpose of review This review seeks to describe the role of the asialoglycoprotein receptor (ASGR) in modulating non-HDL lipoprotein levels, platelet numbers and atherosclerosis. Recent findings Genetics studies have revealed that ASGR haplodeficiency provides protection from atherosclerosis. The potential interactions of ASGR with LDL receptor may regulate the rate of LDL uptake and as a result may lower plasma non-HDL cholesterol. ASGR clears senescent platelets and induces the expression of hepatic thrombopoietin. Platelet activity promotes plaque formation and atherosclerosis. Summary ASGR is a multifunctional receptor specializing in clearance of desialylated glycoproteins and platelets. The impact of ASGR on the levels of plasma non-HDL cholesterol makes it a potential therapeutic target for the treatment of hypercholesterolemia and atherosclerosis.