Glutamate Transporters-1 (GLT-1), also recognised as Excitatory Amino Acid Transporter 2 (EAAT2)are essential for managing glutamate levels in the central nervous system. In the brain, GLT-1 is mainly responsible for glutamate clearance from the synaptic cleft. Brain tissue can accumulate extracellular glutamate by inhibiting glutamate uptake into glial cellsdue to the inhibition of GLT-1 on neuronal glial cells. Hippocampal GLT-1 upregulations canalleviate cognitive dysfunctions in neurodegenerative conditions like amyotrophic lateral sclerosis, Parkinson’s, Alzheimer's disease, etc.The aetiology of GLT-1 impairment in these conditions encompasses oxidative stress, inflammation, and genetic alterations. Oxidative stress can potentially harm GLT-1 by diminishing its ability to efficiently uptake glutamate. Neuroinflammatory pathways may decrease GLT-1 expression and operation, exacerbating excitotoxic injury. Genetic mutations that impact the regulation of GLT-1 can hinder its function, resulting in heightened extracellular glutamate concentrations and consequent neurotoxic effects. Due to the critical role of GLT-1 in preventing excitotoxicity, researchers are investigating various therapeutic methods to boost its effectiveness. By utilizing pharmacological compounds enhancing GLT-1, there is a possibility of lowering glutamate levels and providing protection against excitotoxicity, ultimately slowing down the neurodegenerationprocess. Ongoing research aims to explore the regulatory processes involved in the expression and operation of GLT-1 to create specific treatments and detect early biomarkers for disease progression. This study describes the regulatory mechanism of neuronal glutamate production and its potential therapeutic application in treating neurodegenerative conditions.