Lta4h, short for leukotriene A4 hydrolase, is a bifunctional zinc metallo-enzyme. It is classically known for its epoxide hydrolase activity, converting leukotriene A4 to the neutrophil chemoattractant LTB4. It is also involved in the metabolism of polyunsaturated fatty acid (PUFA), specifically in the arachidonic acid (AA) metabolism pathway. Lta4h has been implicated in the regulation of various biological processes and is associated with many diseases, such as chronic lung diseases and cancers [1,2,3,4,5,6].

In hepatocellular carcinoma (HCC), Lta4h is downregulated. Lta4h-deficient mice show exacerbated hepatocyte damage by restraining JNK activation and increased CD206+ macrophage polarization via upregulation of LTBP1 and downstream TGF-β secretion. Mechanistically, Lta4h induces HNRNPA1 phosphorylation, affecting Ltbp1 mRNA maturation. Lta4h-deficient patients have poor prognosis and immunotherapy resistance [1]. In skin cancer, Lta4h knockout significantly reduces skin cancer development in a mouse model. Lta4h depletion decreases skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase through enhancing p27 protein stability [4]. In ovarian cancer, Lta4h deficiency enhances sensitivity to Cisplatin and modifies immune cell infiltration characteristics [5].

In conclusion, Lta4h plays crucial roles in multiple biological processes, especially in cell cycle regulation and immune microenvironment modulation. Gene knockout mouse models have revealed its significance in cancer development and treatment response, providing insights into potential diagnostic and therapeutic strategies for Lta4h-related diseases, particularly in HCC, skin cancer, and ovarian cancer.