Ankyrin repeat domain-containing protein 1, or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene also known as CARP. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies. Structure Human cardiac ankyrin repeat protein is a 36.2kDa protein composed of 319 amino acids., though in cardiomyocytes, CARP can exist as multiple alternatively spliced forms. CARP contains five tandem ankyrin repeats. Studies have shown that CARP can homodimerize. Studies have also shown that CARP is N-terminally, post-translationally cleaved by calpain-3 in skeletal muscle, suggesting alternate bioactive forms of CARP exist. CARP has been localized to nuclei and Z-discs in animal and human muscle cells, and at intercalated discs in human cardiac muscle cells. Function CARP was originally identified as a YB-1-associating, cardiac-restricted transcription co-repressor in the homeobox NKX2-5 pathway that is involved in cardiac ventricular chamber specification, maturation and morphogenesis, and whose mRNA levels are exquisitely sensitive to Doxorubicin, mediated through a hydrogen peroxide/ERK/p38MAP kinase-dependent as well as M-CAT cis-element-dependent mechanism. Subsequent studies showed that CARP expression in cardiomyocytes is regulated by alpha-adrenergic signaling, in part via the transcription factor GATA4. An additional study showed that beta-adrenergic signaling via protein kinase A and CaM kinase induces the expression of CARP, and that CARP may have a negative effect on contractile function. CARP has also been identified as a transcriptional co-activator of tumor suppressor protein p53 for stimulating gene expression in muscle; p53 was found to be an upstream effector of CARP via upregulation of the proximal ANKRD1 promoter. CARP has a relatively short half-life being longer in cardiomyocytes than endothelial cells; and CARP is degraded by the 26S proteasome via a PEST degron. In animal models of disease and injury, CARP has been characterized to be a stress-inducible myofibrillar protein. CARP has been shown to play a role in skeletal muscle structure remodeling, and repair, being expressed in skeletal muscle near myotendinous junctions, and in vascular smooth muscle cells, as a downstream target of TGF-beta/Smad sigmaling in response to balloon injury and atherosclerotic plaques. Further studies have identified a role for CARP in initiation and regulation of arteriogenesis. Decreased expression of CARP in cardiac cells within the ischemic region was detected in a rat