Abstract
Phosphorylase kinase is a four‐subunit enzyme involved in the regulation of glycogen breakdown. The traditional textbook view is that only the γ subunit has enzymatic activity, whereas the other three subunits have a regulatory role. Evidence from homology searches and sequence alignments, however, shows that the α‐ and β‐subunits possess amino‐terminal glucoamylase‐like domains and suggests that they might possess a previously overlooked amylase activity. If true, this would have important implications for the understanding, diagnosis, and management of glycogen storage diseases. There is thus a clear need to test this hypothesis through enzymatic assays and structural studies.