For example, chronic stress increases ER dysfunction and leads to protein homeostasis diseases, such as aging-associated Alzheimer’s or Parkinson’s disease, metabolic diseases, amyotrophic lateral sclerosis, etc. Chaperones and foldases, such as GRP78 and PDI, play protective roles by reducing protein aggregation, increasing ER function, maintaining proteostasis, or reducing ER stress. This evidence concerns the gene P4HB and Parkinson disease.