Because of its role in synaptic plasticity, glutamate is involved in cognitive functions such as learning and memory in the brain.

[2] The form of plasticity known as long-term potentiation takes place at glutamatergic synapses in the hippocampus, neocortex, and other parts of the brain.

[3] In addition, glutamate plays important roles in the regulation of growth cones and synaptogenesis during brain development.

Glutamate is a very major constituent of a wide variety of proteins; consequently it is one of the most abundant amino acids in the human body.

[5] The mechanisms of cell death include Excitotoxicity due to excessive glutamate release and impaired uptake occurs as part of the ischemic cascade and is associated with stroke,[9] autism,[10] some forms of intellectual disability, and diseases such as amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease.

Microinjection of glutamic acid into neurons produces spontaneous depolarisations around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks.

This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage-activated calcium channels, leading to glutamic acid release and further depolarization.

[citation needed] Glutamate functions as a neurotransmitter in every type of animal that has a nervous system, including ctenophores (comb jellies), which branched off from other phyla at an early stage in evolution and lack the other neurotransmitters found ubiquitously among animals, including serotonin and acetylcholine.

[15] The genome of Trichoplax, a primitive organism that also lacks a nervous system, contains numerous metabotropic glutamate receptors, but their function is not yet known.

One of the most common reasons for skepticism was the universality of glutamate's excitatory effects in the central nervous system, which seemed inconsistent with the specificity expected of a neurotransmitter.