CREB1 and Down syndrome: Moreover, DYRK1A phosphorylates several transcriptional factors, such as CREB and NFAT, endocytic complex proteins, and AD-linked gene products, RCAN1 is an endogenous inhibitor of calcineurin A, and its unbalanced activity is thought to cause major neuronal and/or non-neuronal malfunction in Down syndrome and Alzheimer disease.