The authors show that reduced endogenous mouse CRB2 levels in Müller cells lacking CRB1 (Crb1KOCrb2LowMGC) results in a retinitis pigmentosa (RP) phenotype, the CRB1-RP mouse retina is more sensitive to chemically induced stress (DL-AAA), and AAV-hCRB2 therapy to Müller cells protects against retinal degeneration and vision deficits in DL-AAA-exposed CRB1-RP mice. Here, CRB2 is linked to retinal degeneration.