Adipophilin, as a lipid droplet-associated protein, is a specific marker in the accumulation of lipid, the overexpression of Adipophilin can promote the accumulation of lipids, which is relevant to the pathological process of atherosclerosis and insulin resistance. Neutral cholesterol ester hydrolase （NCEH） is a microsomal enzyme and richly expressed in human atheromatous lesions, can hydrolyze cholesterol ester （CE） in a neutral pH environment, and plays a rate-limiting role in the reverse transportation of cholesterol esters. Adipophilin and NCEH plays an opposite role in maintaining the dynamic balance between the formation and hydrolysis of lipid drops. Under the pathological state, the dynamic balance between Adipophilin and NCEH is broken, thus the accumulation of cholesterol ester is promoted, and the occurrence and development of atherosclerosis is further accelerated. However, the mechanism of Adipophilin and NCEH in the formation and hydrolysis of lipid drops, and their role in the occurrence and development of atherosclerosis, is still unclear. So, this paper is reviewed about this issue.