EIF2AK4 and neuropathy: Importantly though, even though the iPSC model may have also led to the discovery of ISR activation, the in vivo animal models were necessary to show that GCN2/ISR inhibition was an effective treatment for neuropathy given that in other neurodegenerative conditions it has been found that activation of the ISR is actually neuroprotective (Ishimura et al., 2016; Sidoli et al., 2016).