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     Western blot analysis of APOC3 expression in human plasma lysate.    

  
  

APOC3 (apolipoprotein C3) is a key protein involved in lipid metabolism, primarily synthesized in the liver and secreted into the bloodstream. It plays a critical role in regulating triglyceride-rich lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), the enzyme responsible for breaking down triglycerides in lipoproteins, and by impairing hepatic uptake of remnant particles. Elevated APOC3 levels are associated with hypertriglyceridemia, a risk factor for cardiovascular diseases (CVD), pancreatitis, and metabolic disorders. Genetic studies linking APOC3 loss-of-function mutations to reduced triglycerides and lower CVD risk have highlighted its therapeutic potential.

APOC3-targeted antibodies and related therapies aim to neutralize or suppress APOC3 activity, thereby enhancing LPL function and promoting triglyceride clearance. Monoclonal antibodies and antisense oligonucleotides (ASOs), such as volanesorsen, have been developed to inhibit APOC3 expression or function. Clinical trials have demonstrated significant triglyceride-lowering effects in patients with severe hypertriglyceridemia or familial chylomicronemia syndrome. However, challenges remain, including balancing efficacy with safety profiles—some therapies have shown side effects like thrombocytopenia. Ongoing research explores novel approaches, including RNA-based therapies and gene editing, to achieve sustained APOC3 suppression. By targeting APOC3. these therapies hold promise for reducing cardiovascular risk and improving outcomes in metabolic diseases, though long-term safety and broader clinical applicability require further investigation.