GABRD encodes the delta subunit of the GABA type A receptor (GABAAR), a pentameric chloride channel fundamental to GABAergic inhibitory neurotransmission in the brain 1. The delta subunit forms functional channels that selectively permit chloride ion flow across neuronal membranes in response to GABA binding 1. Unlike synaptic receptors, delta-containing GABAARs localize to extrasynaptic positions in hippocampus and cerebellar granule cells, mediating tonic rather than phasic inhibition 1. These receptors may simultaneously bind GABA and histamine, potentially regulating sleep-wake cycles 1. GABRD mutations cause developmental and epileptic encephalopathies through gain-of-function mechanisms affecting extrasynaptic GABAAR signaling 2. GABRD loss in 1p36 deletions contributes to seizures, developmental delay, and psychomotor retardation in affected individuals 34. Polymorphisms in GABRD associate with childhood-onset mood disorders, particularly in males 5. Beyond neurotransmission, GABRD exhibits oncogenic properties in gastric and colon cancers. In gastric cancer, elevated GABRD promotes proliferation and migration through CCND1-dependent mechanisms while suppressing p53-dependent apoptosis 6. In breast cancer, GABRD activation downstream of GPT2-derived GABA initiates PKC-CREB signaling, driving metastasis via calcium channel activation 7. This dual role—essential for normal inhibitory neurotransmission yet pathogenic when dysregulated—positions GABRD as a therapeutic target across neurological and malignant diseases.