Objective To assess the role of transient receptor potential channel mucolipin 1(MCOLN1)in the formation of aortic plaque in atherosclerotic mice and investigate the mechanism.Methods Wild-type C57BL/6 and ApoE-/-mice were divided into four groups:control,model,MCOLN1 overexpression,and overexpression negative control groups.An atherosclerosis model was established by feeding the mice with a high-fat diet.Oil red O and hematoxylin-eosin(HE)staining were used to determine the histopathological changes of the aorta.Western blot and immunofluorescence staining were used to detect the expressions of related proteins and autophagy markers,and evaluate the effect of MCOLN1 expressions on macrophage autophagy and atherosclerosis.Results Overexpression of MCOLN1 reduced aortic lipid accumulation,inhibited plaque formation,and attenuated the development of atherosclerosis.MCOLN1 improved lysosomal function,promoted macrophage autophagy,and inhibited cellular foaminess.Conclusion MCOLN1 has been found to decelerate the progression of atherosclerosis by promoting macrophage autophagy,which provides new potential drug targets for the prevention and treatment of atherosclerosis.