MAF1 is a negative regulator of RNA polymerase III (Pol III) transcription that suppresses production of transfer RNAs, 5S rRNA, and other small non-coding RNAs in response to cellular stress and nutrient availability 12. Mechanistically, MAF1 associates with the Pol III clamp to impair its recruitment to promoter-bound transcription initiation complexes 3. The mTOR kinase directly phosphorylates MAF1; nutrient availability maintains MAF1 phosphorylation and allows Pol III transcription, while stress-induced dephosphorylation promotes nuclear localization and Pol III repression 45. Beyond Pol III regulation, MAF1 modulates Pol I and Pol II-dependent transcription, repressing TATA-binding protein and fatty acid synthase while activating the tumor suppressor PTEN 6. MAF1 dysregulation associates with multiple diseases: upregulation exacerbates Alzheimer's disease through NMDAR1 regulation and synaptic dysfunction 7, while loss accelerates hepatocarcinogenesis 8. MAF1 suppresses sepsis-associated encephalopathy by inhibiting NF-κB-mediated NLRP3 inflammasome activation 9. Recent findings reveal MAF1's broader metabolic roles in lipid homeostasis, connecting RNA and lipid metabolism dysregulation to obesity and cancer pathogenesis 1011.