MAT2A encodes methionine adenosyltransferase 2A, a rate-limiting enzyme that catalyzes S-adenosylmethionine (SAM) synthesis from methionine and ATP 1. SAM is the principal biological methyl donor required for diverse cellular processes including DNA methylation, RNA modification, and protein synthesis 2. MAT2A is expressed in most extrahepatic tissues and plays critical roles in metabolic homeostasis 2. Mechanistically, mTORC1 signaling stimulates MAT2A expression through c-MYC, linking cell growth to SAM availability and m6A RNA methylation 3. METTL16 regulates MAT2A expression through SAM-sensing mechanisms, enabling cells to maintain proper methyl donor levels under nutrient stress 4. MAT2A has emerged as a therapeutic target in MTAP-deleted cancers, where synthetic lethality mechanisms enable selective growth inhibition 56. MAT2A inhibition reduces PRMT5 activity and induces DNA damage and senescence in cancer cells 67. In CNS inflammation, MAFG cooperates with MAT2A to promote DNA methylation and pro-inflammatory transcriptional programs in astrocytes, linking MAT2A to multiple sclerosis pathogenesis 8. These findings position MAT2A as both a metabolic hub regulating cell growth and a promising anticancer target, with clinical candidates currently in trials.