ALKBH1 is a Fe(II) and α-ketoglutarate-dependent dioxygenase with diverse enzymatic functions in nucleic acid metabolism 1. Its primary catalytic activity involves demethylation of multiple substrates: it removes N1-methyladenine from tRNAs (particularly at position 58), catalyzes oxidation of mitochondrial tRNA(Met) to form 5-formylcytosine at wobble positions, and demethylates N6-methyladenosine (m6A) in DNA and mRNA 2. ALKBH1 regulates translation initiation and elongation in response to metabolic stress, with mitochondrial tRNA modifications expanding codon recognition to include AUA alongside AUG 1. Clinically, ALKBH1 dysregulation associates with multiple disease states. In chr14 kidney disease, ALKBH1-mediated 6mA demethylation facilitates Oct4 binding to BMP2 promoters, driving osteogenic reprogramming of vascular smooth muscle cells and vascular calcification 3. In acute myeloid leukemia, ALKBH1 overexpression is essential for leukemia stem cell self-renewal and confers venetoclax resistance through tRNA-decoding reprogramming and codon-biased translation 2. In glioblastoma, elevated N6-mA regulated by ALKBH1 promotes tumor proliferation 4. Additionally, ALKBH1 possesses non-catalytic functions, regulating HIF-1α stability and glycolysis through N-glycosylation modulation 5. These findings position ALKBH1 as a promising therapeutic target across multiple malignancies and metabolic diseases 1.