Ephx2, also known as epoxide hydrolase 2, encodes a 11,12-EET-hydrolytic enzyme. It is involved in the arachidonic acid (AA) metabolic pathway [1,3]. By hydrolyzing epoxyeicosatrienoic acids (EETs) to less active dihydroxyeicosatrienoic acids, Ephx2 diminishes the benefits of EETs, which have effects like coronary vasodilation and protection against post-ischemic mitochondrial damage [4].

In various disease models, Ephx2 has shown significant impacts. In muscle regeneration, deletion of Ephx2 led to the accumulation of 11,12-EET, which accelerated muscle regeneration, and EPHX2 accumulation in aged muscle was reversed by 11,12-EET treatment [1]. In cardiac ischemia-reperfusion, disruption of Ephx2 in cardiomyocytes (but not endothelial cells) improved functional recovery in isolated mouse hearts [4]. In Alzheimer's disease, EPHX2 may mediate pathogenesis by affecting the entire hippocampal volume, and no potential side-effects of targeting it were found [2]. In prostate cancer, EPHX2 was frequently deleted, and its decreased expression was correlated with the Gleason grade and disease-free survival time [3]. In colon cancer, EPHX2 was shown to inhibit tumor progression by promoting fatty acid degradation [5]. In hepatocellular carcinoma, down-regulation of EPHX2 was associated with disease development, and it was identified as an independent prognostic biomarker [6].

In conclusion, Ephx2 plays a crucial role in multiple biological processes and disease conditions. Gene-knockout or conditional-knockout mouse models have been instrumental in revealing its functions in muscle regeneration, cardiac function after ischemia-reperfusion, Alzheimer's disease, prostate cancer, colon cancer, and hepatocellular carcinoma. Understanding Ephx2's functions provides insights into disease mechanisms and potential therapeutic targets.