APOA5 (apolipoprotein A5) serves as a critical regulator of plasma triglyceride metabolism through its interaction with lipoprotein lipase (LPL) and the angiopoietin-like protein 3/8 complex (ANGPTL3/8). The protein functions by binding to ANGPTL3/8 and suppressing its inhibitory effect on LPL activity, thereby promoting triglyceride hydrolysis 1. APOA5 deficiency leads to increased ANGPTL3/8 activity, reduced LPL levels in tissue capillaries, and subsequent hypertriglyceridemia 1. Complete deficiency causes severe type V hyperlipidemia, while heterozygous mutations predispose individuals to hypertriglyceridemia 2. The carboxyl-terminal domain is essential for function, as truncated forms lacking lipid-binding domains cannot regulate triglyceride levels effectively 21. Clinically, APOA5 polymorphisms are significantly associated with metabolic syndrome, with variants like rs662799 increasing disease risk by approximately 1.4-fold 34. These polymorphisms also confer increased susceptibility to cardiovascular diseases, including coronary heart disease and ischemic stroke 56. The c.553G>T variant shows particularly strong association with hypertriglyceridemia in Asian populations 7.