Recent studies also support the notion that although the short-term induction of RCAN1 expression generally has a protective effect in multiple cell types by inhibiting the calcineurin/NFAT transcriptional pathway [16,43], chronic overexpression of RCAN1 may drive pathophysiological changes in neurons and endocrine cells linked to Down syndrome, Alzheimer’s disease and Type 2 diabetes [17,44,45]. Here, RCAN1 is linked to early-onset autosomal dominant Alzheimer disease.