ALDH1L1 is a cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide, serving as a key regulatory enzyme controlling one-carbon flux in folate-dependent biosynthetic pathways 1. The gene is predominantly expressed in astrocytes throughout the brain and serves as an astrocyte-selective marker, making it valuable for genetic targeting of astrocytes in vivo 23. In disease contexts, ALDH1L1 shows divergent roles. In cancer, ALDH1L1 is typically downregulated via promoter methylation in malignant tumors and is considered a candidate tumor suppressor; gossypol-mediated inhibition of ALDH1L1 impairs NADPH and ATP production in non-small cell lung cancer cells 14. Conversely, astrocytic ALDH1L1 expression facilitates neuroinflammatory pathways—selective removal of astrocytic APOE4 in ALDH1L1-expressing astrocytes markedly reduced tau-mediated neurodegeneration and pTau pathology, suggesting astrocyte-specific roles in Alzheimer's disease 5. Additionally, ALDH1L1 gene polymorphisms (rs4646733, rs2305225, rs2276731) are associated with increased neural tube defect risk in the Chinese population 6, implicating folate metabolism in developmental neurobiology.