Gldc, or glycine decarboxylase, is a core enzyme in the glycine cleavage system located on the mitochondrial membrane. It is responsible for regulating glycine levels, contributing one-carbon units to folate metabolism, and is crucial for normal development and metabolism [3].

Mutations in Gldc are the main cause of classic nonketotic hyperglycinemia (NKH), with 80% of subjects in a study having Gldc mutations [1]. In a zebrafish model of Gldc deficiency, embryos showed renal, craniofacial, and neural development defects, indicating its essential role in renal progenitor patterning during kidney development [3].

In cancer research, in prostate cancer, Gldc plays a central role in glycolysis, enhances aerobic glycolysis, and promotes cell migration, invasion, and immune escape [2]. In TNBC, Gldc is up-regulated, promotes cell proliferation, and is correlated with tumor immune infiltration [4]. In colorectal cancer, Gldc promotes metastasis through the Hippo signaling pathway-mediated epithelial-mesenchymal transition [5].

In conclusion, Gldc is essential for regulating glycine metabolism and has a significant impact on development and disease. Its role in NKH and various cancers, as revealed by genetic models such as zebrafish and through studies in human subjects, provides valuable insights into potential therapeutic targets for these diseases.