Kim_2026_Korean.J.Physiol.Pharmacol__

Paraoxonase 2 (PON2) is an enzyme exhibiting both lactonase and esterase activities, widely distributed across various tissues and localized within cellular mitochondria. It plays a vital role in innate immunity by restricting bacterial infections and has diverse functions, including the regulation of mitochondrial reactive oxygen species levels and the management of endoplasmic reticulum stress. By alleviating oxidative stress, stabilizing mitochondria, and modulating apoptosis, PON2 emerges as a significant factor in the study of cellular senescence. This review consolidates recent findings regarding PON2's physiological roles, its mechanistic connections to senescence, and the therapeutic potential of modulating its activity. Our analysis highlights PON2's considerable promise as a target for aging-related diseases, including neurodegeneration, metabolic disorders, cardiovascular diseases, chronic inflammation, and cancer.