Aldh1l1, also known as cytosolic 10-formyltetrahydrofolate dehydrogenase, is a regulatory enzyme in folate metabolism. It controls the flux of one-carbon groups in folate-dependent biosynthetic pathways, which are crucial for nucleic acid biosynthesis, DNA repair, methylation processes, amino acid biogenesis, and energy balance [1,3].

In cancer research, Aldh1l1 is often down-regulated in human cancers, mainly through promoter methylation [1,2,3]. In a diethylnitrosamine (DEN) model of liver carcinogenesis, knockout of Aldh1l1 in mice (Aldh1l1-/-) promoted liver tumor growth without affecting tumor initiation or multiplicity, suggesting that its loss provides a metabolic advantage for tumor progression at a later stage [2,5]. Additionally, in non-small cell lung cancer cells, gossypol can bind to Aldh1l1, disrupt folate metabolism, and exert anti-cancer effects by blocking NADPH and ATP production [4].

In conclusion, Aldh1l1 is essential in folate metabolism, regulating one-carbon group flux. Gene knockout mouse models, like the Aldh1l1-/-mice in liver carcinogenesis, have revealed its potential role as a tumor suppressor. These in vivo studies emphasize the significance of Aldh1l1 in cancer development, highlighting its potential as a target for cancer therapy [2,4,5].