EAAT4

EAAT4, or excitatory amino acid transporter 4, is a member of the solute carrier family SLC1 and is encoded in humans by the SLC1A6 gene. It is a neuronal glutamate transporter with the highest expression in the cerebellum, particularly in Purkinje cells, and to a lesser extent in other brain regions. Its presence in cerebellar circuits positions it to influence motor coordination and synaptic signaling.

Functionally, EAAT4 is a high-affinity, sodium- and proton-coupled transporter that clears glutamate from the synaptic cleft by cotransporting Na+ and H+ with glutamate and counter-transporting K+. In addition to substrate transport, EAAT4 mediates a rapid, substrate-activated anion conductance, mainly for chloride, which can affect neuronal excitability. The protein is generally thought to form trimers in the membrane, with each subunit capable of functioning independently.

Cellular localization and regulation of EAAT4 emphasize its role in modulating synaptic transmission. It is found on dendritic membranes of neurons, especially in cerebellar Purkinje cells, and its surface expression is subject to activity-dependent regulation and intracellular signaling pathways. Interactions with scaffolding and signaling proteins influence its trafficking and function.

Clinical relevance remains an area of active research. Altered EAAT4 function has been explored in cerebellar disorders and seizure models in animals, and while some human associations have been suggested, robust clinical links are not yet established. Research continues to clarify its contribution to cerebellar physiology and pathophysiology.