GYS2 encodes hepatic glycogen synthase, which catalyzes the transfer of glucose from UDP-glucose to the growing α-1,4-glucan chain, extending the glycogen primer initiated by glycogenin. The enzyme is regulated by circadian oscillations controlled by BMAL1, with rhythmic expression patterns synchronized across the 24-hour cycle 1. Biallelic GYS2 variants cause glycogen storage disease type 0 (GSD0), an autosomal recessive disorder characterized by markedly decreased or absent hepatic glycogen synthase activity 2. Affected individuals present with hyperketotic hypoglycemia during fasting and postprandial hyperglycemia; seizures are common and often misdiagnosed as epilepsy until hypoglycemia is identified as the underlying cause 34. Cornstarch and protein-rich diets effectively prevent hypoglycemic episodes and support normal neurocognitive development 2. Beyond monogenic disease, GYS2 functions as a tumor suppressor in hepatocellular carcinoma. Expression is significantly downregulated in HCC, and GYS2 stabilizes p53 by competitively binding MDM2 to prevent p53 ubiquitination and degradation 5. GYS2 overexpression inhibits HepG2 cell proliferation and migration via p53-dependent mechanisms 1. Circadian dysregulation of GYS2 may contribute to HCC progression, as loss of BMAL1-mediated rhythmic control associates with the steatosis-to-carcinoma transition 1. GYS2 knockdown accelerates tumor growth in vivo, whereas overexpression provides resistance to metabolic stress 6.