GNPDA2 (glucosamine-6-phosphate deaminase 2) is an enzyme that catalyzes the reversible conversion of glucosamine-6-phosphate to fructose-6-phosphate in the hexosamine biosynthesis pathway, playing a crucial role in metabolic regulation. The enzyme functions as a key regulatory node connecting glucose and amino sugar metabolism, with high expression levels in hypothalamus and adipose tissue 1. GNPDA2 significantly impacts adipogenesis and lipid metabolism, as overexpression enhances lipid droplet accumulation while knockdown decreases it, affecting genes involved in thermogenesis, PPAR signaling, and fatty acid metabolism 2. The gene responds to nutritional status, with expression decreasing during fasting in hypothalamus and increasing in adipose tissue under high-glucose-fat diet conditions 3. Central nervous system GNPDA2 does not control appetite but regulates glucose homeostasis, as its inhibition results in glucose intolerance 1. Genetic variants in GNPDA2, particularly rs10938397, are consistently associated with obesity risk and body mass index across multiple populations including Japanese and Chinese cohorts 45. Recent evidence suggests GNPDA2 may also be involved in neurodegenerative processes, with elevated serum levels observed in multiple neurological proteinopathies including Alzheimer's disease 6.