ANGPTL3 and familial hypercholesterolemia: Although neutralizing antibodies targeting ANGPTL3 have been approved to reduce lipoprotein levels in individuals with homozygous familial hypercholesterolemia, the inhibition of hepatic ANGPTL3 using antisense oligonucleotide (ASO) drug Vupanorsen unexpectedly led to liver lipid accumulation, ultimately resulting in the termination of the clinical trial49,50.