PHKG2 encodes the catalytic gamma subunit of phosphorylase kinase, a key regulator of glycogen breakdown. In its canonical role, PHKG2 phosphorylates and activates glycogen phosphorylase to mediate neural and hormonal regulation of glycogenolysis 1. The protein functions as part of the phosphorylase kinase complex in the cytosol and may also regulate glycogenolysis in testicular tissue 2. Beyond glycogen metabolism, PHKG2 has emerged as a critical regulator of ferroptosis, an iron-dependent form of regulated cell death. PHKG2 controls iron availability to lipoxygenase enzymes, which peroxidize polyunsaturated fatty acids to drive ferroptosis 3. In head and neck squamous cell carcinoma, TP53 transcriptionally activates PHKG2, which then phosphorylates PPP1R3B to enhance protein phosphatase 1 activity, ultimately promoting NRF2 nuclear export and ferroptosis 4. Clinically, mutations in PHKG2 cause glycogen storage disease type IXc (GSD IXc), an autosomal recessive disorder characterized by phosphorylase kinase deficiency 1. While generally benign, PHKG2 mutations—particularly missense and nonsense variants in exons 3 and 6 5—are associated with severe hepatic phenotypes including cirrhosis in childhood 26. Additionally, impaired PHKG2-mediated signaling contributes to hepatic insulin resistance in type 2 diabetes 7.