RCAN1 Human

The Regulator of Calcineurin 1 (RCAN1), also known as Down Syndrome Critical Region 1 (DSCR1), is a protein encoded by the RCAN1 gene located on chromosome 21q22. This protein plays a crucial role in various physiological processes, including neurodegeneration, mitochondrial dysfunction, inflammation, and protein glycosylation .

RCAN1 has two main isoforms, RCAN1-1 and RCAN1-4, which result from differential promoter use and first exon choice . These isoforms have distinct functions and regulatory mechanisms. RCAN1-1 consists of 252 amino acids, while RCAN1-4 comprises 197 amino acids .

RCAN1 is an endogenous inhibitor of the serine/threonine phosphatase calcineurin. Calcineurin is a heterodimer composed of a catalytic subunit (calcineurin A) and a regulatory subunit (calcineurin B) . By binding to the catalytic domain of calcineurin A, RCAN1 inhibits calcineurin-dependent transcriptional responses . This inhibition affects various signaling pathways, including the nuclear factor of activated T cells (NFAT) and NF-κB pathways .

RCAN1 is implicated in several diseases, most notably Down syndrome and Alzheimer’s disease. Overexpression of RCAN1 in the brain of Down syndrome fetuses is associated with neurofibrillary tangles, similar to those observed in Alzheimer’s disease . Additionally, RCAN1 plays a role in cardiovascular diseases (CVDs) by participating in the development and functional maintenance of the cardiovascular system .

Recent studies have highlighted the potential of RCAN1 as a therapeutic target. For instance, RCAN1 has been identified as a novel RNA-binding protein that regulates neuronal apoptosis . The discovery of RNA aptamers that block RCAN1-induced inhibition of NFAT and NF-κB signaling pathways offers promising avenues for neuroprotective therapies .