ALKBH5 is an RNA N6-methyladenosine (m6A) demethylase that catalyzes oxidative demethylation of m6A, the most prevalent internal mRNA modification in eukaryotes 1. This process requires molecular oxygen, alpha-ketoglutarate, and iron 1. ALKBH5-mediated m6A demethylation regulates mRNA processing, translation, and export 1, directly impacting gene expression across multiple biological systems. Beyond canonical roles, ALKBH5 participates in paraspeckle assembly through liquid-liquid phase separation 2. Dysregulation of ALKBH5 contributes to multiple diseases: hepatic ALKBH5 upregulation promotes glucose and lipid dysmetabolism in obesity and type 2 diabetes through GCGR and mTORC1 signaling 3; elevated astrocytic ALKBH5 drives depressive-like behaviors by modulating glutamate transporter m6A modification 4; and cardiac macrophage ALKBH5 mediates m6A demethylation of IL-11, promoting pathological cardiac fibrosis 5. In cancer, ALKBH5 exhibits context-dependent roles. Decreased ALKBH5 in gastric cancer promotes invasion via PKMYT1 m6A-dependent regulation 6, while elevated ALKBH5 in colorectal cancer drives immune suppression through AXIN2-Wnt signaling 7. Psychological stress-induced ALKBH5 deficiency in pancreatic cancer enhances tumor innervation via aberrant m6A modification in extracellular vesicles 8. These findings identify ALKBH5 as a therapeutic target across metabolic, neuropsychiatric, and neoplastic disorders.