Phosphorylase is regulated by several allosteric effectors that signal the energy state of the cell and by reversible phosphorylation, wich is responsive to hormones such as insulin, epinephrine, and glucagon.

Skeletal muscle phosphorylase exists in two interconvertible forms: an active phosphorylase a and a usually inactive phosphorylase b. Phosphorylase b is converted into phosphorylase a by the phosphorylation (covalent modification - slow).

Phosphorylase b is active only in the presence of high concentrations of AMP, wich acts allosterically. ATP acts as a negative allosteric effector by competing with AMP. Glucose-6-P also inhibites phosphorylase b.