Triglyceride (TG) is predominantly present in triglyceride-rich lipoproteins (TRLs). Dysregulation of TRL metabolism is closely associated with the occurrence and development of atherosclerosis. Lipoprotein lipase (LPL), a glycoprotein secreted by parenchyma cells, can cleave TG within the TRLs to produce free fatty acid. A variety of factors are involved in TRL metabolism and atherosclerosis progression by regulating LPL expression and activity. Thus, clarifying the role TRL metabolism and its regulatory mechanisms could have significant implications for the prevention and treatment of cardiovascular disease.