Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate. Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production. Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell death. May play a role in mitophagy inhibition. beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate Belongs to the phosphoglycerate mutase family. Not expected to have any kinase activity.