SHMT2, short for serine hydroxymethyltransferase 2, is a key enzyme in one-carbon metabolism. It catalyzes the conversion of serine into glycine and a tetrahydrofolate-bound one-carbon unit, which is crucial for nucleotide biosynthesis, amino acid metabolism, and methylation reactions [1,2,3,4,5,6]. One-carbon metabolism is associated with various biological processes, including cell proliferation, and is thus of great biological importance. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying SHMT2's functions.

In a mouse model with hepatocyte-specific ablation of SHMT2, it was found that the absence of SHMT2 increased serine and glycine levels in circulation, decreased liver methylation potential, and increased susceptibility to fatty liver disease. However, these mice had less inflammation and fibrosis when fed a diet high in fat, fructose, and cholesterol, highlighting SHMT2's stage-specific functions in non-alcoholic fatty liver disease (NAFLD) pathogenesis [6]. In Burkitt lymphoma, inhibition of SHMT2 by knockdown or pharmacological compounds induced anti-lymphoma effects in vitro and in vivo, leading to reduced intracellular glycine and formate levels, inhibiting the mTOR pathway, and triggering autophagic degradation of the oncogenic transcription factor TCF3 [3].

In conclusion, SHMT2 plays essential roles in one-carbon metabolism, which is fundamental for multiple cellular processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases like NAFLD and Burkitt lymphoma. Understanding SHMT2's functions provides insights into disease mechanisms and potential therapeutic targets.