NHE-5 exchanger corrects intracellular acidosis by exporting H+ in exchange for extracellular Na+, thereby tending to raise intracellular pH. Several studies have suggested that NHE5 plays a critical role in the synaptic pH regulation during the firing of action potentials.NHE5 knockdown or overexpression of a dominant-negative mutation of NHE5 in cultured hippocampal neurons causes dendritic spine overgrowth. Therefore it has been suggested that NHE5 acts as a negative regulator of activity-dependent spine growth by regulating pH-sensitive synaptic proteins
