PSENEN and Alzheimer disease: The protein complex γ-secretase (g-sec) is the only known intramembrane protease requiring an elaborate interplay between four different proteins: nicastrin (NIC), presenilin (PS), anterior pharynx-defective-1 (APH-1) and presenilin enhancer-2 (PEN-2) (Bai et al., 2015a,b; Langosch et al., 2015; Langosch and Steiner, 2017), rendering it the structurally most complex member of this functional family and due to its proposed role in Alzheimer's disease (AD) also the most studied one (De Strooper et al., 2012; Fukumori and Steiner, 2016).