AHCY (adenosylhomocysteinase) is a highly conserved enzyme that catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine (SAH) to adenosine and homocysteine 1, serving as the only mammalian enzyme capable of this reaction. As a rate-limiting enzyme in the methionine cycle 2, AHCY regulates cellular methylation by removing SAH, a potent inhibitor of methyltransferases 1. The enzyme facilitates local transmethylation reactions through controlled subcellular localization, being recruited to chr20 during DNA replication and active transcription 1. Beyond canonical methionine metabolism, AHCY catalyzes formation of homocysitaconate, an anti-inflammatory metabolite that increases 152-fold during inflammation and inhibits pro-inflammatory MARS/NLRP3 signaling 3. AHCY dysfunction causes hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency, a rare recessive metabolic disorder 1. Clinically, AHCY is upregulated in colorectal cancer, particularly in APC-deficient tumors, and AHCY inhibition impairs cancer cell growth and reduces tumor burden 4. AHCY inhibition also suppresses adipocyte progenitor proliferation and differentiation through altered DNA methylation 5, while AHCY inhibitors like 3-deazaadenosine alleviate cellular senescence and enhance stem cell therapy efficiency 6. These findings establish AHCY as a critical metabolic hub linking one-carbon metabolism to inflammation, cancer, aging, and cellular differentiation.