Enhanced glutamate mediated excitotoxicity in ALS has been shown to be a combination of excessive pre-synaptic release [67,69] and inhibited uptake from the synaptic cleft due to ineffective astroglial glutamate transporters (EAAT2) observed in the spinal cord [70] and motor cortex of affected ALS patients [71,72] and in rodent models of ALS [73,74,75], resulting in glutamate retention and persistent enhanced post-synaptic NMDA and AMPA receptor activation [67,68], causing an increased intracellular influx of Ca2+ and Na+ ions resulting in a synaptic hyper-active state [69]. The gene discussed is SLC1A2; the disease is amyotrophic lateral sclerosis.