SLC17A8 encodes vesicular glutamate transporter-3 (VGLUT3), a multifunctional transporter essential for glutamatergic synaptic transmission. At synaptic vesicle membranes, VGLUT3 functions as an electrogenic uniporter that loads L-glutamate into vesicles at presynaptic terminals, driven by the proton gradient established by vacuolar H⁺-ATPase 1. The transporter also functions as a chloride channel affecting vesicle acidification and operates synergistically with acetylcholine vesicular transporter in striatal neurons 2. At the plasma membrane, VGLUT3 acts as an electrogenic sodium-phosphate symporter supporting phosphate homeostasis. Unlike VGLUT1 and VGLUT2, VGLUT3 expression is restricted to specific neuronal populations, including cholinergic interneurons and serotonin neurons, suggesting novel roles for glutamate signaling 3. VGLUT3 dysfunction causes autosomal-dominant hearing loss (DFNA25), with heterozygous missense mutations impeding vesicular glutamate accumulation in inner hair cells 4. Loss-of-function mutations lead to auditory neuropathy through defective glutamate release at the inner hair cell synapse 5. Recent evidence demonstrates therapeutic potential: intracisternal delivery of adeno-associated virus carrying SLC17A8 rescued hearing in deaf null mice by restoring VGLUT3 expression in inner hair cells 6. These findings establish SLC17A8 as a target for gene therapy in progressive genetic hearing loss.