ALKBH3 is an alpha-ketoglutarate-dependent dioxygenase that functions as a DNA and RNA demethylase, primarily targeting N1-methyladenosine (m1A) modifications 1. The enzyme removes alkyl damage from DNA, particularly 1-methyladenosine and 3-methylcytosine lesions in single-stranded DNA substrates 2. In RNA metabolism, ALKBH3 demethylates m1A modifications in mRNA, particularly within 5'-untranslated regions near start codons, thereby regulating RNA stability and translation 2. The protein demonstrates context-dependent functions in disease: it can act as a tumor suppressor by maintaining genomic integrity at transcriptionally active promoters in some contexts 3, while promoting oncogenesis in others through metabolic reprogramming and disruption of tumor suppressor pathways 24. ALKBH3 plays a critical role in neurodegeneration by demethylating CAG repeat RNA, where its diminished expression leads to increased m1A levels that promote TDP-43 aggregation and neuronal toxicity 5. Clinically, ALKBH3 expression is dysregulated across multiple cancers and is subject to epigenetic silencing 6. Its involvement in metabolic feedback loops, particularly through lactate-mediated histone modifications, positions it as a potential therapeutic target in age-related diseases and cancer 4.