BCL2 and Alzheimer disease: Over the years, it has become clear that deranged neuronal Ca2+ signaling is a very early hallmark of AD pathology, thereby driving pathogenesis.455,456 Hence, strategies to normalize or preserve Ca2+ signaling hold therapeutic promise to delay the deleterious impacts of AD progression.457–459 At the mechanistic level, both excessive Ca2+ release through IP3Rs460–462 and ryanodine receptors,463–468 potentially related in part to BCL2 downregulation, have been implicated in AD.