As Ca2+ dyshomeostasis is found in AD and P86L‐CALHM1 is considered a risk factor for AD, we investigated how native CALHM1 and P86L‐CALHM1 could contribute to Ca2+ homeostasis, survival signaling pathways (namely, ERK and the transcription factor CREB), and cell survival at baseline or after treatment with Aβ. This evidence concerns the gene CREB1 and Alzheimer disease.