Aldehyde dehydrogenase family 1 member L2 (ALDH1L2)

Aldehyde dehydrogenase family 1 member L2 (ALDH1L2) is a mitochondrial enzyme that catalyzes the NADP⁺-dependent oxidation of 10-formyltetrahydrofolate to tetrahydrofolate and CO₂, thus participating in mitochondrial one-carbon metabolism[1][3]. ALDH1L2 plays a crucial role in regulating the mitochondrial pool of one-carbon units, supporting metabolic pathways such as fatty acid β-oxidation and influencing the distribution of one-carbon groups between mitochondria and cytosol[5]. Unlike its cytosolic homolog (ALDH1L1), ALDH1L2 is retained in various tumor types and has been implicated in cancer cell proliferation, tumor-associated macrophage polarization, and chemoresistance—especially in hepatocellular carcinoma, where its high expression is associated with poor prognosis and reduced cancer sensitivity to drugs like sorafenib[2]. Inhibition or knockdown of ALDH1L2 enhances chemosensitivity and modulates tumor immune microenvironment, highlighting its potential as both a therapeutic target and biomarker in oncology[2][4].

Other names

Mitochondrial 10-formyltetrahydrofolate dehydrogenasemtFDHMitochondrial 10-FTHFDHFLJ38508Probable 10-formyltetrahydrofolate dehydrogenase ALDH1L2

Enzyme inhibition: Drugs that inhibit ALDH1L2 sensitize cancer cells to chemotherapy (e.g., sorafenib, 5-fluorouracil)