GLDC (glycine decarboxylase) is a mitochondrial enzyme that serves as the P protein component of the glycine cleavage system, catalyzing the degradation of glycine by binding its alpha-amino group through a pyridoxal phosphate cofactor and releasing CO2 1. The gene spans at least 135 kb with 25 exons and is expressed in liver, kidney, brain, and placenta 1. GLDC functions in glycine catabolism and one-carbon metabolism, with deficiency leading to nonketotic hyperglycinemia (NKH), a severe neurological disorder caused by glycine accumulation 23. In NKH, 80% of cases involve GLDC mutations, with over 484 unique mutations identified 2. Beyond metabolic function, GLDC exhibits diverse physiological roles: it negatively regulates antiviral responses, with higher expression increasing susceptibility to severe influenza 4, and protects against cisplatin-induced kidney injury by modulating UCP1-mediated pathways 5. GLDC also demonstrates oncogenic properties in cancer, promoting cell proliferation and tumorigenesis 67, while playing protective roles in liver ischemia-reperfusion injury by inhibiting macrophage recruitment 8. Gene therapy approaches using AAV vectors show promise for treating NKH by restoring GLDC function 3.