Yang and colleagues demonstrate that lipid nanoparticle-mediated precise hepatic ASGR1 base editing safely produces robust and durable lipid lowering in an LDLR-deficient mouse model of familial hypercholesterolemia. Their work further benchmarks the lipid-lowering effects of ASGR1 and ANGPTL3 editing and supports combined ASGR1/ANGPTL3 targeting for enhanced cholesterol lowering.