Bifunctional epoxide hydrolase 2

Bifunctional epoxide hydrolase 2 (EPHX2) is a 555-amino acid enzyme with dual catalytic activities: the C-terminal domain hydrolyzes epoxides and arene oxides in xenobiotic metabolism, while the N-terminal domain functions as a lipid phosphatase targeting phosphorylated lipids including lyso-glycerophospholipids and related metabolites (UniProt: P34913). These activities position EPHX2 in detoxification and lipid signaling pathways, regulating both exogenous toxic compounds and endogenous physiological mediators.

EPHX2 is broadly expressed and implicated in lipid metabolism and inflammatory responses through its phosphatase activity on bioactive lipids. The protein lacks disease annotations in the UniProt record but shows proteomics evidence of dysregulation in Alzheimer's Disease.

In Alzheimer's Disease, EPHX2 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.875 (Chaparral AD proteomics). This upregulation was observed in TMT-labeled quantitative proteomics across subcellular fractions, suggesting potential involvement in AD-associated lipid metabolism or detoxification dysregulation. The biological significance of this elevation in AD pathology requires further investigation.