In the present study, we demonstrated for the first time that CTRP12 mitigates atherosclerosis by promoting ABCA1/ABCG1-dependent cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα signaling pathway, thereby providing a novel target for the prevention and treatment of atherosclerotic cardiovascular disease. This evidence concerns the gene C1QTNF12 and atherosclerosis.