GAPDH, short for Glyceraldehyde-3-phosphate dehydrogenase, is a prominent housekeeping protein and a key enzyme in energy metabolism. It catalyzes the sixth step in glycolysis, generating NADH and playing a regulatory role in anaerobic glycolysis. The triose substrate of GAPDH is a product of multiple metabolic pathways, and its reaction is reversible, thus crucial for hepatic gluconeogenesis. GAPDH is involved in various biological processes beyond glycolysis, and its study using genetic models can provide insights into its functions [1,3,4,5,6].

GAPDH is ubiquitously highly expressed in most cancer types, and high expression in tumor tissues is associated with poor prognosis. Pan-cancer analysis indicates it may contribute to multiple cancer-related pathways, and its overexpression is regulated by DNA copy number amplification and promoter methylation modification. A transcription factor, FOXM1, can regulate GAPDH expression and is highly expressed in multiple cancer types [2]. In neuroblastoma, GAPDH has a key role in metabolism and survival, stimulating glucose uptake at the plasma membrane and activating autophagy through a nuclear complex with Sirtuin [4].

In conclusion, GAPDH is essential for energy metabolism and participates in numerous biological processes. Its study, especially through models like gene knockout in mice (not directly mentioned in the references but in the context of genetic models), could potentially shed light on its role in diseases such as cancer, where its dysregulation is implicated in tumor development and prognosis.