Heather et al. suggested that altered APP processing, as observed in AD, may disrupt PI(3,5)P2 metabolism, endosomal sorting, and homeostasis since APP binding to the PIKfyve complex [consist of PIKfvye (also known as Fab1), Vac14 (ArPIKfyve), and Figure 4 (Sac3)] drives formation of PI(3,5)P2 positive vesicles (33). This evidence concerns the gene VAC14 and Alzheimer disease.