The finding that the ISR is similarly activated in both Gars and Yars mutant mice suggests that this mechanism may be in play across the tRNA synthetase-associated neuropathies, though this remains to be tested for mutations in HARS, WARS and AARS. Furthermore, though the Gars/CMT2D mouse models accurately recapitulate the human disease, it also remains to be determined whether the same ISR mechanism is active in human motor and sensory neurons. This evidence concerns the gene AARS1 and neuropathy.