We demonstrated that (1) LMP10 is highly expressed in lesional macrophages in diet-induced atherosclerosis; (2) LMP10 deletion, especially myeloid-specific LMP10 deletion, attenuates diet-induced atherosclerosis; and (3) LMP10 deletion might inhibit NF-κB-mediated macrophage polarization and inflammation. Here, PSMB10 is linked to atherosclerosis.