Angiopoietin-like 3 protein (ANGPTL3) is an inhibitor of both lipoprotein lipase 
and endothelial lipase in humans. Population studies indicate a relationship 
between loss of function mutations in ANGPTL3 and favorable reductions in 
triglycerides and non- high-density lipoprotein cholesterol. In addition, loss 
of function mutations is associated with a reduced risk of coronary artery 
disease. Whereas ANGPTL3's role in human lipid metabolism has yet to be fully 
clarified, it is unlikely that ANGPTL3 impacts cholesterol uptake via the 
low-density lipoprotein-receptor, unlike the proprotein convertase 
subtilisin/kexin9 inhibitors. In contrast to other forms of lipid-lowering 
therapy, ANGPTL3 inhibition may improve insulin sensitivity. The promise of this 
new therapy, particularly its independence from the low-density 
lipoprotein-receptor, has prompted the creation of a monoclonal antibody 
inhibitor; evinacumab. Evinacumab has shown favorable lipid-lowering action in 
both human and mouse models. Efficacy trials are currently ongoing and will be 
completed in the near future. In addition, ANGPTL3 inhibition via an antisense 
oligonucleotide was performed in healthy human subjects, which resulted in a 
dose-dependent reduction in circulating ANGPTL3 levels and an antiatherogenic 
lipid profile. When tested in mouse models, administration of the antisense 
oligonucleotide caused a reduction in progression of atherosclerosis. Further 
investigation is required to evaluate the efficacy, safety and net benefit of 
clinical ANGPTL3 inhibition before it can be accepted into clinical practice.