GABBR2 encodes the gamma-aminobutyric acid type B receptor subunit 2, which forms a functional heterodimeric G-protein coupled receptor with GABBR1 for the inhibitory neurotransmitter GABA 1. While GABBR1 binds agonists, GABBR2 mediates G-protein coupling and downstream signaling pathways that inhibit adenylate cyclase, modulate ion channels, and regulate neurotransmitter release, playing a critical role in synaptic inhibition 2. The receptor functions both pre- and post-synaptically to fine-tune inhibitory transmission in the nervous system 2. Disease relevance is significant, as de novo mutations in GABBR2 cause developmental and epileptic encephalopathy 59 (EIEE59) and neurodevelopmental disorders with features resembling Rett syndrome, including epilepsy, intellectual disability, and motor dysfunction 13. These mutations typically reduce receptor expression and GABA-mediated inhibition, leading to seizures and developmental regression 2. Clinical significance extends beyond neurological disorders, with GABBR2 showing roles in cancer metastasis through transcriptional regulation mechanisms 4, angiogenesis regulation via glycolysis pathways 5, and immune homeostasis in the gut 6. The gene is also implicated in nicotine dependence susceptibility 7.