PON2, a member of the paraoxonase gene family along with PON1 and PON3, is a lactone hydrolyzing enzyme. It has various functions such as hydrolyzing acyl-homoserine lactones involved in bacterial quorum-sensing, controlling oxidative stress, inhibiting apoptosis, and influencing the progression of malignancies. PON2 also shows anti-inflammatory properties and is expressed in brain tissue, with unique sub-cellular localization primarily in mitochondria where it scavenges superoxides [1,2].

PON2-deficient (PON2-def) mice have been used to study its role. These mice are more susceptible to diet-induced obesity, with increased body weight due to fat mass gain, adipocyte hypertrophy, and impaired glucose tolerance. They also have decreased oxygen consumption and energy expenditure, along with reduced beige adipocyte markers in subcutaneous fat pads [4]. In B-cell acute lymphoblastic leukemia (B-ALL), genetic deletion of Pon2 in mouse models compromised leukemia cell proliferation, colony formation, and leukemia initiation, as PON2-deficient cells had defective glucose uptake and ATP production [5]. In Ang II-induced cardiomyocyte injury, PON2 can ease the injury by targeting the CANX/NOX4 signaling pathway [3].

In conclusion, PON2 plays crucial roles in multiple biological processes. Studies using PON2 KO mouse models have revealed its significance in obesity, leukemia, and cardiomyocyte injury. Its functions in oxidative stress control, apoptosis inhibition, and influence on disease progression make it an important gene for understanding disease mechanisms and potentially developing new treatment strategies.