Atherosclerosis is a chronic inflammatory process where lipids accumulate along the arterial wall. One key protein in atherosclerosis development is AIBP (Apolipoprotein A-I binding protein). AIBP exists both inside and outside cells, but only secreted AIBP is well characterized in atherosclerosis. A recent study found that AIBP is highly expressed in human and mouse atherosclerotic lesions and that the AIBP was concentrated within the inner membrane of macrophage mitochondria. Macrophages are immune cells that can have pro- or anti-inflammatory phenotypes. The interplay between these phenotypes plays a pathogenic role in atherosclerosis. In this study, blocking the production of AIBP in bone marrow aggravated atherosclerosis and increased macrophage infiltration in a mouse model. This bone-marrow-specific AIBP deficiency increased the cleavage of the protein PINK1 (PTEN-induced putative kinase 1). Increased PINK1 cleavage then decreased the normal breakdown of damaged mitochondria (mitophagy), which caused the macrophages to polarize to their pro-inflammatory phenotype. These findings describe a new role for AIBP in atherosclerosis, where its deficiency in macrophages drives inflammation by impairing mitophagy and suggest that AIBP is a promising treatment target for diseases that are characterized by macrophage-driven inflammation, like atherosclerosis.