EAAT1

The excitatory amino acid transporter 1 (EAAT1, also known as GLAST or SLC1A3) is a high-affinity Na⁺-dependent glutamate transporter primarily expressed in astrocytes, where it regulates extracellular glutamate concentrations and prevents excitotoxic neuronal damage^[1][2][3]. Mechanistically, EAAT1 mediates glutamate uptake by coupling the transport of glutamate with Na⁺ and K⁺ ions, enabling clearance against steep concentration gradients and maintaining synaptic homeostasis^[3][4]. Compared with EAAT2, EAAT1 exhibits a more restricted spatial distribution, with higher expression in spinal cord laminae 1-3 and in cerebellar glial populations, and demonstrates a unique substrate- and Na⁺-independent leak conductance that distinguishes it from neuronal isoforms EAAT3-EAAT5^[5][4]. In disease models, EAAT1 dysregulation is implicated in neurodegenerative disorders, psychiatric conditions, and platelet dysfunction, indicating its role in both central and peripheral glutamate handling^[6][7][8]. Recent studies reveal that EAAT1 expression is crucial for the proliferation and survival of T-cell acute lymphoblastic leukemia (T-ALL), where it supports glutamine-derived aspartate synthesis and nucleotide production, highlighting its potential as a therapeutic target^[9]. Pharmacological inhibition using selective antagonists, such as UCPH101, demonstrates EAAT1’s dominant role in glutamate clearance at glial synapses, in contrast to other EAAT subtypes which show secondary or context-dependent activity^[10].