Recently, additional roles, including involvement in STIM1-Orai1-Coupling and Store-operated Calcium Entry23, autophagy33, DNA binding34, and inflammatory-related functions35, have been reported for RTNs, and their involvement in neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as hereditary spastic paraplegia36, are evident. Here, ORAI1 is linked to early-onset autosomal dominant Alzheimer disease.