The mechanism underlying the paradoxical loss of Aldob and up-regulated glycolysis in HCC tumor cells has not been defined until our recent study identified a novel tumor-suppressive mechanism by which Aldob directly binds and inhibits the rate-limiting enzyme in pentose phosphate pathway (PPP), glucose-6-phosphate dehydrogenase (G6PD) [18]. This evidence concerns the gene ALDOB and hepatocellular carcinoma.