ALKBH2 is a DNA repair enzyme that catalyzes the direct reversal of alkylated nucleic acid bases through oxidative dealkylation 1. The enzyme functions as a dioxygenase, using molecular oxygen, 2-oxoglutarate, and iron as cofactors to oxidize alkyl groups, which are subsequently released as aldehydes, thereby regenerating undamaged bases 1. ALKBH2 demonstrates substrate specificity for monoalkylated bases, particularly N1-methyladenine and N3-methylcytosine, and can repair higher-order alkyl adducts including etheno adducts 1. The enzyme shows strong preference for double-stranded DNA substrates and acts by probing base pair stability, locating weakened base pairs, and flipping damaged bases into its active site for catalysis. ALKBH2 plays a critical role in cellular resistance to alkylating agents, with deficiencies rendering cells more sensitive to methylating chemotherapy 2. Clinically, ALKBH2 is relevant in cancer biology, where its overexpression contributes to chemotherapy resistance 3. The enzyme's expression is dynamically regulated in viral infections, being suppressed in HTLV-1 carriers but restored in acute T-cell leukemia patients 4. Germline variants in ALKBH2 have been associated with early-onset lung adenocarcinoma risk, particularly in Asian populations 5. The enzyme can be stabilized by USP7, which prevents its proteasomal degradation and contributes to temozolomide resistance in glioblastoma 6.