GAD1 encodes glutamate decarboxylase 1 (GAD67), a key enzyme catalyzing GABA synthesis from glutamate 1. While classically known for its neurotransmitter role in the brain, GAD1 has emerged as a metabolic hub with broader pathophysiological significance. In cancer contexts, aberrant GAD1 expression rewires glutamine metabolism to synthesize GABA, which activates GABAB receptors to enhance β-catenin signaling, promoting tumor proliferation and suppressing CD8+ T cell infiltration 2. Similarly, PMVK-mediated stabilization of GAD1 increases GABA conversion to 4-acetaminobutyric acid, an immunosuppressive metabolite that inhibits CD8+ T cell activation through GABAA receptors 3. Beyond cancer, B cell-derived GABA (synthesized via GAD67) promotes anti-inflammatory macrophage differentiation while suppressing CD8+ T cell function 4. In the nervous system, NG2 glia-derived GABA release via GAD67 modulates inhibitory synaptic transmission and contributes to stress-induced anxiety 5. Clinically, reduced GAD1 expression in prefrontal cortex associates with schizophrenia, involving epigenetic dysregulation, aberrant chr2 architecture, and alternative splicing disruption 167. These findings reveal GAD1 as a multifunctional regulator integrating metabolic, immunological, and neurobiological processes with relevance to cancer, immunotherapy resistance, and psychiatric disease.