LDLR (low-density lipoprotein receptor) is a cell surface receptor primarily responsible for clearing circulating low-density lipoprotein (LDL) cholesterol from the bloodstream through receptor-mediated endocytosis 1. The receptor internalizes LDL particles, which are degraded in lysosomes while LDLR itself recycles back to the cell surface via a SNX17-dependent mechanism in acidic endosomes 2. This recycling process is critical for maintaining hepatic LDLR abundance and circulating cholesterol homeostasis 3. PCSK9 protein inhibits LDLR by preventing SNX17-mediated recycling, causing LDLR degradation in lysosomes and elevated LDL-cholesterol levels 2. Loss-of-function LDLR mutations cause familial hypercholesterolemia, characterized by severe hypercholesterolemia and premature atherosclerotic cardiovascular disease 3. Beyond lipid metabolism, LDLR serves as an entry receptor for multiple viral pathogens, including Crimean-Congo hemorrhagic fever virus, using its ligand-binding domain for viral glycoprotein interaction 4. Clinically, LDLR variants associate with variable disease severity and response to PCSK9 inhibitors, with recycling-defective variants conferring PCSK9-inhibitor resistance 2. All approved lipid-lowering medications aim to increase LDLR surface availability to enhance LDL clearance 3.