Since eIF2 is essential for most forms of translation initiation and therefore protein synthesis, defects in eIF2 are often lethal. The protein is highly conserved among evolutionary remote species - indicating a large impact of mutations on cell viability. Therefore, no diseases directly related to mutations in eIF2 can be observed. However, there are many illnesses caused by down-regulation of eIF2 through its upstream kinases. For example, increased concentrations of active PKR and inactive (phosphorylated) eIF2 were found in patients with neurodegenerative diseases such as Alzheimers, Parkinsons, and Huntingtons disease. There is also one proven example of a disease related to the GEF eIF2B. Mutations in all of the five subunits of eIF2B are associated with Vanishing White Matter (VWM) disease, a genetic leukodystrophy which causes the brains white matter to degenerate and disappear. It is still not fully understood why only brain cells seem to be affected by these defects. Potentially reduced levels of unstable regulatory proteins might play a role in the development of the diseases mentioned.