Glutamic acid decarboxylase 65 (GAD65) is an enzyme that synthesizes the inhibitory neurotransmitter 纬-aminobutyric acid (GABA) from glutamate, playing a crucial role in the central nervous system. It is one of the two isoforms of glutamic acid decarboxylase, the other being GAD67. GAD65 is particularly notable for its dynamic structure and its role as a major autoantigen in type 1 diabetes (T1D), with autoantibodies against it often present before the clinical onset of the disease. Structurally, GAD65 forms obligate functional dimers and consists of three domains: the N-terminal domain (NTD), the pyridoxal-5'-phosphate (PLP)-binding domain, and the C-terminal domain (CTD). Its catalytic loop (CL) is dynamic, which contrasts with the stable conformation of GAD67's CL.