AD causing mutations in presenilin 1 blocks this Ca2+-leak activity thereby causing ER Ca2+-overload with detrimental effects on ER-dependent signaling affecting store operated Ca2+ entry (SOCE), expression of ryanodine receptors (RyR), and inositol trisphosphate receptors (IP3R) (Blalock et al., 2003; Emilsson et al., 2006; Bezprozvanny, 2009; Popugaeva and Bezprozvanny, 2014). Here, PSEN1 is linked to Alzheimer disease.