Tkt, or transketolase, is a key enzyme in the non-oxidative phase of the pentose phosphate pathway (PPP), a branch of glycolysis. This pathway is crucial for cancer cell survival and biosynthesis, highlighting the importance of Tkt in metabolism [5]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying Tkt's functions.

In liver-specific Tkt overexpression and knockout mouse models, Tkt was found to be sufficient and required for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Tkt deletion increased hepatic inosine levels, which activated a cascade leading to improved mitochondrial function [1]. In intestinal epithelial cell-specific Tkt-deficient mice, they suffered from growth retardation and spontaneous colitis. Tkt deficiency led to altered metabolite levels, reduced ATP production, excessive apoptosis, and a defective intestinal barrier [2]. Lentivirus-mediated Tkt knockdown in murine hearts after myocardial infarction (MI) ameliorated cardiomyocyte apoptosis and preserved systolic function, while overexpression had the opposite effect. Inducible conditional cardiomyocyte Tkt-knockout mice further confirmed Tkt's role in ischemic heart failure [3]. Tkt knockdown also inhibited the tumor growth of xenograft T-cell acute lymphoblastic leukemia (T-ALL) mice [4].

In conclusion, Tkt plays essential roles in metabolism-related biological processes and disease conditions. Through the use of KO/CKO mouse models, its functions in diseases like MAFLD, colitis, ischemic heart failure, and T-ALL have been revealed. These studies provide a better understanding of the underlying mechanisms and potential therapeutic targets for these diseases.