PHKB encodes the beta regulatory subunit of phosphorylase kinase, a tetrameric enzyme complex that activates glycogen phosphorylase to regulate glycogen breakdown 1. The beta subunit acts as a regulatory component that modulates holoenzyme activity in response to phosphorylation 2. The human PHKB gene is located on chromosome 16-q13, consists of 33 exons spanning at least 140 kb, and shows 95% amino acid sequence identity with rabbit 21. Mutations in PHKB cause glycogen storage disease type IXb, characterized by hepatomegaly, elevated transaminases, ketotic hypoglycemia, and poor growth 34. Novel pathogenic variants can result in severe liver involvement and cirrhosis 4. Beyond its metabolic role, PHKB functions as a tumor suppressor in hepatocellular carcinoma, with decreased expression associated with poor prognosis 5. PHKB overexpression inhibits cell proliferation, invasion, and epithelial-mesenchymal transition through inactivation of AKT and STAT3 signaling pathways, independent of glycogen metabolism 5. Deficiencies in PHKB can also affect skeletal muscle, contributing to exercise-induced symptoms in glycogen metabolism disorders 6.