Besides preexisting metabolic disease, changes in lipoprotein composition and circulating lipid content, either due to altered intrahepatic processing or due to changes in cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and proprotein convertase subtilisin/kexin type 9 (PCSK9) activity in plasma, are a mainstay in patients with severe systemic inflammation. The gene discussed is PCSK9; the disease is inflammation.