Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.

Glutamine: fructose-6-phosphate amidotransferase (GFAT), a conserved enzyme across prokaryotic and eukaryotic species, is the first and rate-limiting step in the hexosamine biosynthetic pathway (HBP), diverting 2–5% of fructose-6-phosphate derived from glucose toward the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a key substrate for the glycosylation of proteins and lipids. While substantial progress has been made in elucidating the basic biochemical properties and regulatory mechanisms of GFAT, its functional impact on pathological processes remains incompletely understood. Emerging evidence implicates GFAT in a spectrum of human diseases, including cancer, diabetes, cardiovascular disorders, and neurodegenerative conditions such as Alzheimer’s disease. This review aims to provide a comprehensive synthesis of current insights into GFAT’s role in disease etiology, with the goal of informing future research and therapeutic strategies targeting this essential metabolic regulator.