Macrophage paraoxonase 2 regulates calcium homeostasis and cell survival under endoplasmic reticulum stress conditions and is sufficient to prevent the development of aggravated atherosclerosis in paraoxonase 2 deficiency/apoE−/− mice on a Western die

► Paraoxonase 2 (PON2) deficiency causes impaired macrophage function. ► PON2 deficiency also exacerbates the development of atherosclerosis. ► In this report, we show that PON2 modulates calcium homeostasis in macrophages. ► PON2 modulates the crosstalk between ER and mitochondria in macrophages. ► Restoration of macrophage PON2 in PON2-def mice prevents atherosclerosis.