When one examines the situation in AMD, it has been postulated that dimethylfumarate, a protector of RPE cells from oxidative injury [87], can be sensed by the Cys-151 modification, whereas cadmium, a potential promoter of AMD which is present in cigarette smoke, is a Cys-151, 273 and 288-independent activator of KEAP1-NFE2L2 pathway [84,88]. Here, KEAP1 is linked to age-related macular degeneration.