MAT2B encodes the regulatory β-subunit of methionine adenosyltransferase 2 (MAT2A), a non-catalytic protein essential for S-adenosylmethionine (SAM) synthesis 1. As a regulatory subunit, MAT2B modulates MAT2A catalytic activity by increasing its affinity for L-methionine and stabilizing the enzyme protein in an NADP+-dependent manner 23. Beyond enzymatic regulation, MAT2B stabilizes MAT2A protein levels, connecting SAM synthesis to mRNA m6A methylation—a process critical for epigenetic gene regulation 2. Mechanistically, MAT2B interacts with MAT2A with high binding affinity (Kd ~6 nM), preventing enzyme degradation at physiological temperatures 3. Additionally, MAT2B serves as a scaffold protein that recruits signaling molecules; it directly interacts with GIT1 and MEK1/ERK to promote cell growth signaling 4. Clinically, MAT2B is frequently upregulated in multiple cancers including liver, colon, endometrial, and osteosarcoma, promoting proliferation through EGFR/PCNA and mTORC1 pathways 56. In liver disease, elevated MAT2A/MAT2B expression through FOXM1 transcriptional regulation drives inflammation and fibrosis 7. MAT2B inhibitors like JX24120 suppress cancer cell viability by blocking SAM synthesis, suggesting therapeutic potential 6.