PYGL, short for glycogen phosphorylase L, is a key enzyme in the glycogen metabolism pathway, specifically involved in glycogenolysis. It mobilizes glycogen to fuel glycolysis, thus playing a crucial role in glucose metabolism regulation. This process is associated with multiple cellular functions and is of great biological importance [1,3,4,7,8].

In pancreatic cancer, PYGL overexpression promotes cell migration, invasion, and liver metastasis, while knockdown has opposite effects. Hypoxia can induce PYGL expression in a HIF1α -dependent manner, leading to glycogen accumulation and subsequent induction of the epithelial-mesenchymal transition (EMT) process through glycolysis, which is related to tumor invasion and metastasis [1].

In head and neck squamous cell carcinoma (HNSCC), PYGL is identified as a metabolism-related oncogenic biomarker promoting tumor progression, metastasis, and chemotherapy resistance via the GSH/ROS/p53 pathway [2].

In gliomas, high PYGL expression is an independent predictor of poor prognosis, and it is involved in glioma cell proliferation, glycolysis, apoptosis, and metabolic activities. Hypoxia-induced PYGL expression regulated by HIF1α also plays a role in glioma progression [5,6,8].

Moreover, PYGL mutations can cause glycogen storage disease type VI, mainly characterized by hepatomegaly, growth retardation, and elevated liver transaminases in untreated children [9].

In conclusion, PYGL is essential for glucose metabolism, with its function intricately linked to the progression of various cancers like pancreatic, HNSCC, and glioma, as well as in glycogen storage diseases. Studies on PYGL, especially through gene-knockout or conditional-knockout models (not explicitly detailed in these references but generally valuable for such gene-function studies), can provide insights into the underlying mechanisms of these diseases, potentially guiding the development of new therapeutic strategies.