Phosphorylase kinase catalytic subunit gamma-2 (PHKG2)

Phosphorylase kinase catalytic subunit gamma-2 (PHKG2) is the catalytic gamma subunit of phosphorylase kinase, a hexadecameric enzyme complex essential for initiating glycogen breakdown by phosphorylating glycogen phosphorylase. PHKG2 encodes the liver- and testis-specific isoform of this enzyme, mediating the regulatory effect of neural and hormonal signals on glucose mobilization. The gamma subunit contains the enzymatic activity, while regulatory alpha, beta, and delta (calmodulin) subunits control it through phosphorylation and calcium sensitivity. PHKG2 deficiency leads to glycogen storage disease type IXc (autosomal liver glycogenosis), characterized by enlarged liver, hypoglycemia, and potential progression to fibrosis or cirrhosis. Recent research suggests PHKG2 may influence cell death pathways (such as ferroptosis) in liver and gastric cancer models, but no targeted drugs exist for this protein

Other names

Phosphorylase kinase, gamma 2 (testis/liver)Phosphorylase b kinase gamma catalytic chain, liver/testis isoformPHK-gamma-LTPHK-gamma-TPSK-C3GSD9CPhosphorylase kinase subunit gamma-2Serine/threonine-protein kinase PHKG2

Not established for any approved drug. Theoretical: Enzyme activation/inhibition through modulation of PHKG2’s kinase activity, targeting the glycogenolysis pathway