Aldehyde dehydrogenase 1 family member L1 (ALDH1L1)

Aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is a cytosolic enzyme crucial for folate metabolism, as it catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate into tetrahydrofolate, NADPH, and carbon dioxide[1][3][5]. It is a member of the aldehyde dehydrogenase superfamily and is best recognized as a robust pan-astrocyte marker in the central nervous system[1][6]. ALDH1L1 modulates cellular energetic and biosynthetic pathways, influencing apoptosis, cell proliferation, and cell motility—functions that support a tumor suppressor-like role, especially as its loss of expression is associated with cancer progression[1][2][3][4]. Genome-wide association studies link ALDH1L1 variants with altered methionine metabolism and increased risk of ischemic stroke[1]. In cancer, particularly lung adenocarcinoma, ALDH1L1 upregulation is linked to KRAS mutations, and combined inhibition with ALDH inhibitors (such as gossypol) and oxidative phosphorylation inhibitors (such as phenformin) synergistically reduces tumor growth[2]. Its high specificity in astrocytes also enables its use as a genetic tool in neuroscience for targeting or tracing astrocyte populations[6]. Deficiencies can result in abnormal folate and one-carbon metabolism, with clinical associations ranging from methanol poisoning susceptibility to certain neurodevelopmental and dermatologic disorders[3][5].

Other names

Cytosolic 10-formyltetrahydrofolate dehydrogenaseFTHFD10-FTHFDHFDH10-fTHFMER57B-ALDH1L1

Inhibition of NAD(P)+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate, NADPH, and CO₂; Suppression of ATP production via blockade of oxidative phosphorylation (when combined with metabolic drugs)