-Dependent and -independent pathways to control circulating low-density lipoprotein (LDL) levels. LDL can be controlled by inhibiting production or by enhancing clearance. Another pathway that controls circulating LDL is by inhibiting the absorption of dietary cholesterol through the inhibition of Niemann–Pick C1-Like1 (NPC1L1). By inhibiting cholesterol synthesis via HMGCOA reductase, apoB synthesis, and formation of hepatic VLDL, the secretion of VLDL can be reduced. LDL receptor is the main player in the removal of circulating LDL. PCSK-9 also contributes to LDL concentration indirectly by influencing the degradation of low-density lipoprotein receptor (LDLR). The inhibition of both apoCIII and ANGPTL3 increases LPL activity, which in turn, hydrolyzed triglycerides in the highly atherogenic lipoproteins, TRL, and increases the uptake of apoB-containing lipoproteins by the liver. Thus, by enhancing the LDLR activity via inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) and accelerating the clearance of atherogenic triglyceride-rich lipoproteins (TRL) by inhibiting apoCIII and angiopoietin-like 3 (ANGPTL3), the levels of LDL can be reduced, which leads to protection from atherosclerotic cardiovascular disease.