There is evidence that overexpression of both STIM2 and Orai1 increased neuronal Ca2+ level; however, no sign of neurodegeneration was observed, suggesting a dissociation of SOCE machinery with Alzheimer’s disease progression as determined by amyloidogenesis and immunohistochemistry (Majewski et al., 2020). Here, STIM2 is linked to early-onset autosomal dominant Alzheimer disease.