ALDH1L2 is a mitochondrial enzyme that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide, playing a crucial role in folate metabolism and cellular redox homeostasis 1. The enzyme generates NADPH, which is essential for antioxidant defense and maintaining cellular redox balance 12. ALDH1L2 also regulates the production of formate for nucleotide synthesis and formyl-methionine for mitochondrial protein translation 1. In cancer biology, ALDH1L2 exhibits complex roles: its loss promotes metastasis in breast cancer by increasing formate and formyl-methionine production, leading to enhanced cell migration through formyl-peptide receptor signaling 1. Conversely, ALDH1L2 supports chemoresistance in small cell lung cancer by interacting with the thioredoxin-peroxiredoxin antioxidant network to inhibit ferroptosis 3, while decreased expression in colorectal cancer correlates with radioresistance 4. Clinically, ALDH1L2 deficiency causes severe neurodevelopmental disorders characterized by reduced NADPH/NADP+ ratios, decreased mitochondrial ATP, and altered metabolism 5. The enzyme also participates in renal fibrosis regulation through microRNA-mediated pathways 6. These findings establish ALDH1L2 as a critical metabolic regulator with significant implications for cancer therapy and genetic disease.