Excitatory amino acid transporter 2

Excitatory amino acid transporter 2 (EAAT2, encoded by SLC1A2) is a sodium-dependent, high-affinity glutamate transporter that mediates the uptake of L-glutamate, L-aspartate, and D-aspartate from the extracellular space (UniProt: P43004). The protein functions as a symporter, coupling amino acid transport to the influx of two or three sodium ions and one proton, with concurrent potassium counter-transport. EAAT2 is essential for rapid clearance of released glutamate from the synaptic cleft and termination of glutamatergic neurotransmission (UniProt: P43004).

EAAT2 is predominantly expressed in glial cells (particularly astrocytes) throughout the central nervous system, where it plays a critical role in glutamate homeostasis. Mutations in SLC1A2 are associated with developmental and epileptic encephalopathy 41 (DEE41), an autosomal dominant disorder characterized by refractory seizures and neurodevelopmental impairment (UniProt: P43004, MIM 617105).

In Alzheimer's disease, EAAT2 protein levels are significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: 0.98, Chaparral AD proteomics). This elevation was detected across subcellular fractions in human post-mortem AD brain using quantitative proteomics, suggesting a potential compensatory response to glutamatergic dysfunction or neuroinflammation characteristic of AD pathology.