Shmt1, also known as cytoplasmic serine hydroxymethyltransferase, is an enzyme that interconverts serine and glycine in one-carbon metabolism [2]. This process is crucial for various biological functions such as development, the immune system, and cancer, as it provides one-carbon units for nucleotide synthesis and cellular methylation reactions [4].

Shmt1 disruption in mice leads to neural tube defects (NTDs) in response to maternal folate and choline deficiency, suggesting its role in folate-responsive NTD pathogenesis by impairing thymidylate biosynthesis [5]. In hepatocellular carcinoma (HCC), loss-of-function experiments show that reduced Shmt1 enhances cell metastatic ability, while overexpression inhibits migration and invasion, indicating its role as a suppressor of HCC metastasis [1]. In renal cell carcinoma (RCC), overexpression of Shmt1 suppresses RCC proliferation and migration, and knockdown of its regulator HOXD8 decreases Shmt1 expression, accelerating RCC growth [3].

In conclusion, Shmt1 plays essential roles in one-carbon metabolism, and its disruption in mouse models reveals its significance in neural tube development and cancer. Specifically, in NTDs, Shmt1 affects thymidylate biosynthesis, and in HCC and RCC, it influences cancer cell metastasis and proliferation respectively. These findings provide insights into the biological functions of Shmt1 and potential therapeutic targets for related diseases.