ALKBH4 is an Fe(II)- and 2-oxoglutarate-dependent dioxygenase that functions as a dual-substrate demethylase with complex roles in cancer biology 1. The enzyme mediates demethylation of both protein and DNA substrates: it removes monomethyl groups from lysine-84 on actin, regulating actomyosin dynamics during cytokinesis and cell migration, and demethylates N6-methyladenine (6mA) in DNA 2. Mechanistically, ALKBH4 couples substrate oxidation to decarboxylation of 2-oxoglutarate to succinate and requires an intact histidine-carboxylate site for productive Fe binding 1. The protein interacts with transcription-associated proteins and localizes to the nucleus, suggesting involvement in gene expression regulation 3. ALKBH4 also modulates DNA cytosine methylation by regulating DNMT1 protein levels 2. In cancer, ALKBH4 exhibits context-dependent roles: it acts as a tumor suppressor under hypoxic conditions by inhibiting epithelial-mesenchymal transition and metastasis 4, while promoting tumorigenesis in other contexts through mechanisms involving reduced 6mA methylation and inhibition of pyroptosis 56. ALKBH4 is overexpressed in various cancers including lung, gastric, and salivary gland tumors, with potential prognostic significance 78.