Activation of the ISR kinase PERK has been linked to retinal degeneration in patients with Retinitis pigmentosa, diabetic retinopathy, macular degeneration and other ocular disorders (PMC6583901). However, the precise molecular mechanism(s) by which PERK activation affects retinal degeneration remain unknown. Retinal degeneration is faithfully modeled in Drosophila using a misfolding mutant Rhodopsin (Rh-1^G69D) encoded by the endogenous ninaE^G69D allele, which leads to age-dependent (PMC1782370). Loss of translational regulators of the ER stress response pathways exacerbates retinal degeneration in the ninaE^G69D model. An active area of interest to examine how and why translation regulation has this effect using Drosophila genetics and molecular biology. This project is currently funded by a K99/R00 from the NEI.