In the nervous system, SLC7A11 regulates synaptic activity by stimulating extrasynaptic receptors and performs nonvesicular glutamate release.

The inhibition of system Xc- has been found to alter a number of behaviors, which suggests that it plays a key role in excitatory signaling.

SLC7A11 is a member of a heterodimeric Na+-independent anionic amino acid transport system highly specific for cystine and glutamate.

[9][10] There are many mechanisms that exist to regulate the expression of system Xc-, although it is not the sole determinant of extracellular glutamate or intracellular glutathione.

This mechanism of release at the synaptic cleft is partially controlled through the active transport of glutamate out of astrocytes by system Xc-.

[10] It has been demonstrated that, in the embryonic retina, Xc- exchanger is responsible for 50% of total glutamate uptake, representing a Sodium-Independent system within this tissue.

The high activity of Xc- in the retina is correlated to a neuroprotective role, once it can take up excessive extracellular glutamate and provide precursors for the synthesis of Glutathione.

[9] There are neurotoxins, such as BMAA, that can prevent the intake of cystine, which can lead to decreased extracellular glutamate levels and an increase in oxidative stress.

Synthetic small molecules such as erastin, sulfasalazine, and sorafenib can inhibit system Xc- function and induce ferroptosis.

If either of these transporters are impaired, it could result in a disruption in glutamate homeostasis and lead to a variety of CNS disorders[15] It has been found that cocaine produces a decrease in Cystine-Glutamate exchange via system Xc-, leading to a decrease in basal, extra synaptic glutamate levels in the nucleus accumbens core (NAcc) region of the brains of cocaine-withdrawn rats.

Increased levels of glutathione lead to a lower toxicity of methamphetamine and alcohol, and cause a decrease in tumor formation after chronic smoking.

[15] Repeated administration of cocaine causes disruptions in glutamate homeostasis that lead to a decrease in function of EAATs.

An increase in levels of system Xc- has also been found in postmortem schizophrenia patients, indicating that there may have been a decrease in net function of these receptors as well, leading to greater expression.

It has been observed that Schizophrenia patients have a decreased level of glutathione in their prefrontal cortex, further supporting the conclusion that system Xc- may not be functioning properly.

Recent study showed that mRNA expression levels of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients are lower than that of healthy individuals.

[16] The release of glutamate by system Xc- may lead to excitotoxicity, which is initiated by extrasynaptic NMDA receptors and can cause neuronal death.

[17][18] It has been observed that glutamate released from microglia leads to oligodendrocyte death in culture and in the rat optic nerve.

It has been observed that an increase in the expression of Nrf2, a transcription factor for system Xc-, leads to a protective effect in mice with ALS symptoms.

[15] Parkinson's disease may be due to mitochondrial dysfunction or oxidative stress, both of which could be caused by a decrease in glutathione levels.