The ratio of autophagy and proteasome, or “A:P ratio,” influences the clearance of proteins, and the balance is broken when the A:P ratio is overwhelmed in the late stage of ER stress.317 P23H mice experience increased autophagy secondary to ER stress, which leads to proteasome insufficiency and increases retinal degeneration.317 The ATF4/CHOP pathway contributes to impaired autophagy in P23H-accumulated mice through the P53-p38-MAPK-eIF4E cascade and binding to LC3 and p62.313 The downregulation of p62 facilitates the upregulation of keap1 and excessive degradation of antioxidant nrf2. Here, DDIT3 is linked to retinal degeneration.