GFPT1 encodes the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP), catalyzing the formation of glucosamine-6-phosphate from fructose-6-phosphate and glutamine 1. This enzyme is subject to feedback inhibition by UDP-N-acetylglucosamine and is phosphorylated and inhibited by adenylyl cyclase-mediated activation of protein kinase A 1. GFPT1 controls glucose flux into the HBP pathway, thereby regulating the availability of precursors for N- and O-linked protein glycosylation 1. The enzyme plays critical roles in maintaining YAP protein expression through O-GlcNAcylation and influences cellular responses to oxidative stress 1. GFPT1 mutations cause congenital myasthenic syndrome type 12 (CMS12), a neuromuscular disorder characterized by impaired neuromuscular transmission 23. In clinical cohorts, GFPT1 variants represent 7.6% of CMS cases and are associated with limb-girdle phenotypes 4. CMS patients with GFPT1 mutations may experience progressive worsening, with some requiring wheelchair assistance 5. Additionally, GFPT1 expression is reduced in osteoarthritis cartilage, and glutamine supplementation can restore its expression, suggesting therapeutic potential 6.