Activation of Sig1R confers protective benefits in several models of neurodegenerative diseases,21, –23 including retinal diseases.29, , , , , , , , –38 (+)-PTZ, a high-affinity Sig1R ligand, is the prototypical compound used to evaluate Sig1R activation.61 Remarkable cone rescue reported in the rd10 model of retinal degeneration requires the presence of Sig1R for (+)-PTZ to confer neuroprotection because, when absent, (+)-PTZ does not preserve cone function.9 Whether Sig1R can modulate rate or severity of rd10 PRC degeneration had not been addressed. Here, SIGMAR1 is linked to neurodegenerative disease.