EPHX2 encodes soluble epoxide hydrolase (sEH), a bifunctional enzyme with dual catalytic activities. The N-terminal domain possesses lipid phosphatase activity toward phosphorylated lipid metabolites, including phosphonooxy-hydroxy-octadecanoic acids and lyso-glycerophospholipids 123. Critically, EPHX2 catalyzes hydrolysis of 11,12-epoxyeicosatrienoic acid (11,12-EET), a bioactive oxylipin with pro-healing properties 4. Genetic evidence implicates EPHX2 in multiple disease pathways. EPHX2 deletion or inhibition accelerates muscle regeneration and rejuvenates aged muscle by preserving 11,12-EET levels, which amplifies fibroblast growth factor signaling 4. In Alzheimer's disease, EPHX2 emerged as a validated druggable target through Mendelian randomization, potentially mediating pathogenesis via hippocampal volume effects, with no predicted adverse effects 56. EPHX2 polymorphisms associate with cardiovascular disease risk and metabolic traits; the rs751141 variant linked to reduced hydrolase activity shows protective effects against hypertension in Han populations and associations with triglyceride and urate levels 78. Additionally, EPHX2 locus variants associate with cannabis use disorder susceptibility 9. These findings position EPHX2 inhibition as a potential therapeutic strategy for tissue regeneration, neurodegeneration, and cardiovascular disease.