SIGMAR1 and neurodegenerative disease: Retinal neuron death in degenerative diseases, such as RP, involves a variety of pathologic mechanisms, most notably oxidative stress2, –4 and ER stress.58,62 As a putative molecular chaperone, Sig1R has been studied for its role in modulating these mechanisms; experimental evidence suggests that Sig1R activation attenuates both types of stress.9,13,36,63 Oxidative stress leads to activation of the NRF2-KEAP1 pathway.64 We observed a modest increase in NRF2 levels in P21 rd10 mice compared with WT, but significantly higher NRF2 levels in age-matched rd10/Sig1R−/− mice.