PHKA2 encodes the liver α-subunit of phosphorylase kinase, a key regulatory enzyme in carbohydrate metabolism 1. The protein functions as part of the phosphorylase kinase complex, which catalyzes phosphorylation of glycogen phosphorylase to mobilize hepatic glycogen stores and generate energy 2. The PHKA2 gene encodes a 1235 amino acid polypeptide involved in carbohydrate metabolic processes and protein modification 1. PHKA2 mutations cause glycogen storage disease type IXa (GSD IXa), the most frequent liver glycogen storage disease 12. Clinical presentations include hepatomegaly, elevated liver transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth, though phenotypic variability exists 23. Missense mutations can produce variant biochemical phenotypes with tissue-specific enzyme activity differences 4. Rare cases exhibit systemic complications including renal tubular dysfunction, neurological symptoms, or progressive cirrhosis 45. Beyond classical metabolism, emerging evidence suggests PHKA2 participates in glycolipid metabolism regulation via post-translational modification of transcriptional regulators, potentially relevant to glioblastoma pathogenesis 6. Genetic testing enables accurate GSD IXa diagnosis and guides management through dietary intervention and supportive therapy 7.