The aberrant activity of S2R-mediated cellular processes, believed to be triggered by cellular stresses and exacerbated in aged cells, is a hallmark of the dysfunction underlying degenerative diseases, including Alzheimer’s disease, α-synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies, and retinal diseases, such as dry AMD. This evidence concerns the gene TMEM97 and early-onset autosomal dominant Alzheimer disease.