Fructose 2,6-biphosphate is a potent activator of phosphofructokinase. It's not a glycolytic intermediate, but it's synthesized when the concentration of fructose-6-P is very high, and iso is a signal that fructose-6-P must be degraded. F26biP activates phosphofructokinase in liver by increasing its affinity for fructose 6-P and diminuishing the inhibitory effect of ATP.