Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS) share several common pathological characteristics, in particular, the abnormal accumulation of misfolded proteins forming inclusions, where a common role for PDI has been assigned (Kim et al., 2000; Muchowski, 2002; Tuite and Melki, 2007). Here, P4HB is linked to early-onset autosomal dominant Alzheimer disease.