GOT2, also known as Glutamic-oxaloacetic transaminase 2, is a highly tissue-specific gene in the liver. It is a key component of the malate-aspartate shuttle, which is crucial for maintaining intracellular NAD(H) redox balance and amino acid metabolism [7,8]. This shuttle system is involved in transferring reducing equivalents from the cytosol to the mitochondria, thus playing an important role in multiple cellular processes.

In hepatocellular carcinoma (HCC), knockdown of GOT2 in HCC cells promoted proliferation, migration, and invasion, and in mouse models of HCC, loss of GOT2 promoted tumor growth, hematogenous and intrahepatic metastasis. Mechanistically, GOT2 silencing reprogrammed glutamine metabolism to enhance glutaminolysis, nucleotide synthesis, and glutathione synthesis, activating the PI3K/AKT/mTOR pathway [1,6].

In pancreatic cancer, GOT2 was found to act as a nuclear fatty acid transporter binding to and activating the PPARδ nuclear receptor, driving immunosuppression by suppressing T cell-mediated antitumor immunity. Also, in vitro, loss of GOT2 in pancreatic ductal adenocarcinoma (PDA) cells disturbed redox homeostasis and halted proliferation, but this inhibitory effect was not seen in xenograft PDA or autochthonous mouse models, likely due to the influence of the tumor microenvironment [2,3,4].

In addition, in acute allograft rejection, higher expression of GOT2 was associated with the immunological status of patients and showed potential for early-stage diagnosis [5].

In conclusion, GOT2 is essential for maintaining cellular redox balance and amino acid metabolism through its role in the malate-aspartate shuttle. Model-based research, especially gene knockout in mouse models, has revealed its significant roles in cancer progression, including HCC and pancreatic cancer, as well as its potential association with acute allograft rejection. Understanding GOT2 provides insights into disease mechanisms and potential therapeutic targets.