PON2 is an intracellular lactonase enzyme expressed across most tissues, with particularly high levels in brain dopaminergic regions 1. Unlike its homologs PON1 and PON3, PON2 is not associated with high-density lipoprotein but localizes primarily to mitochondria 21. The enzyme hydrolyzes lactones and aromatic esters, including acyl-homoserine lactones involved in bacterial quorum sensing, representing a defense mechanism against pathogens 3. PON2 exerts potent antioxidant and anti-inflammatory properties by scavenging mitochondrial superoxides and preventing lipid peroxidation 12. These antioxidant functions extend to inhibiting endoplasmic reticulum stress-induced apoptosis and protecting against oxidative stress-related toxicity 4. PON2 expression is modulated by estradiol and polyphenols like quercetin, and is sex-dependent, with higher levels in females than males 1. Clinically, PON2 dysregulation has implications for neurodegenerative diseases through mitochondrial biogenesis pathways 5, cardiovascular disease protection, and cancer cell survival through stress resistance mechanisms 6. PON2 may represent a novel therapeutic target for neuroprotective and cardioprotective strategies, with potential gender-specific disease prevention applications.