Excitatory amino acid transporter 4 (EAAT4)

Excitatory amino acid transporter 4 (EAAT4) is a membrane protein encoded by the SLC1A6 gene and is primarily expressed in cerebellar Purkinje cells in the central nervous system[7][3][1]. It functions as a high-affinity sodium-dependent transporter for the excitatory neurotransmitters L-glutamate and L-aspartate, clearing these from the synaptic cleft to prevent neurotoxicity and modulate synaptic transmission[7][5][3]. EAAT4 also exhibits a significant chloride conductance, acting as a glutamate-gated chloride channel, which differentiates it from other EAAT subtypes[5][3]. This transporter is highly localized to specialized neuronal regions and plays a pivotal role in fine-tuning excitatory neurotransmission within the cerebellum[1][7]. Although considered a potential drug target, as of 2024 there are no approved therapies selectively targeting EAAT4, and research is focused on understanding its precise neurological roles and therapeutic potential[6][10][4]. Most clinical interest and drug development are focused on the closely related transporter EAAT2; EAAT4-specific research and selective modulators remain primarily preclinical. Evidence for disease roles is strongest for neurodegenerative and cerebellar dysfunctions where loss or alteration of EAAT4 impacts glutamate homeostasis[5].

Other names

SLC1A6EAAT4Excitatory amino-acid transporter 4Solute carrier family 1 member 6

Drugs targeting EAAT4 can act through transport inhibition, blocking glutamate/aspartate uptake, allosteric modulation (noncompetitive inhibition), or by enhancing chloride conductance (a non-transport effect).