Rescue of enzymatic function for disease-associated RPE65 proteins containing various missense mutations in non-active sites

Background: Disease-causing mutations reduce RPE65 protein levels with unknown mechanisms. Results: Interaction of 26 S proteasome non-ATPase regulatory subunit 13 with mutant RPE65s mediates degradation of misfolded RPE65s via the ubiquitin-proteasome pathway. Conclusion: Many mutant RPE65s with non-active site mutations are catalytically active and can be rescued. Significance: Low temperature and chaperones that rescue enzymatic function of mutant RPE65s are therapeutic candidates.