ROS levels and Ca2+ levels increase dramatically, and then Mekk1 is phosphorylated, which induces cdk5 upregulation, and affects the JNK pathway and has a pro-apoptosis function.305,310,311 Rod photoreceptor death and retinal degeneration then occurs.312,313 In a retinal degeneration 10 model that possesses a PDE6 mutation and is widely used for RP studies, intracellular Ca2+ elevation-related ER stress occurs in the whole layer of the retina even before RP symptoms appear.314 As a result, ER chaperone S1R elevates in abundance to antagonize Ca2+. Here, MAPK8 is linked to retinal degeneration.