Apolipoprotein A5 (ApoA5) is a newly discovered apolipoprotein which is closely associated with high-density lipoprotein (HDL) remodeling. Clinically it demonstrates potent triglyceride reducing effect. Recent studies have found that ApoA5 can increase cholesteroal reverse transportation and HDL function by remodeling HDL, and it can also influence the progression of atherosclerosis in the different ways, showing a potential anti-atherosclerosis effect. Here we briefly review the characteristics of ApoA5 and its potential protective effect against atherosclerosis.