In hippocampal neurons from the PSEN1KI or the APP-knockin (APPKI) mouse models of AD and in human sporadic AD cortical samples, downregulation of STIM2 protein disrupts neuronal SOCE thus inhibiting the continuous Ca2+ influx necessary for sustained calmodulin kinase II (CaMKII) activation that is, in turn, essential for the stability of mushroom spines (Sun et al., 2014). The gene discussed is APP; the disease is Alzheimer disease.