PYGL, short for glycogen phosphorylase L, is an important enzyme in the glycogen metabolism pathway, specifically involved in glycogenolysis. It mobilizes glycogen to fuel glycolysis, thus playing a crucial role in glucose metabolism [1,3,4,7,8]. Glycogen metabolism is significant in many biological processes, and alterations in this pathway can have far-reaching impacts on cell function and disease development. Genetic models, such as KO or CKO mouse models, could potentially be valuable for studying PYGL's functions.

PYGL has been implicated in multiple disease conditions. In pancreatic cancer, its overexpression promotes epithelial-mesenchymal transition (EMT), cell migration, invasion, and liver metastasis. Hypoxia induces PYGL expression in a HIF1α-dependent manner, which then promotes glycogen accumulation and subsequent glycolysis to drive EMT [1]. In head-and-neck squamous cell carcinoma (HNSCC), PYGL is identified as a metabolism-related oncogenic biomarker that promotes tumor progression, metastasis, and chemotherapy resistance through the GSH/ROS/p53 pathway [2]. In gliomas, high PYGL expression is an independent predictor of poor prognosis. It regulates glycolysis and apoptosis under hypoxic conditions, with knockdown of PYGL inhibiting cell invasion, proliferation, and migration while enhancing apoptosis [5,6,7]. Also, mutations in PYGL can lead to glycogen storage disease type VI in children [9].

In conclusion, PYGL is essential for regulating glycogen-based energy metabolism and glucose utilization. Model-based research, especially through KO or CKO mouse models (although not explicitly detailed in the provided references but generally valuable in gene-function studies), could potentially further elucidate its role. PYGL's dysregulation is associated with various cancers and glycogen-storage diseases, highlighting its importance in understanding disease mechanisms and potentially developing targeted therapies.