model of ischemic injury, and was thought to be linked to the induction of GADD153, an apoptosis-related gene. In cardiomyocytes treated with doxorubicin, a model of anthracycline-induced cardiomyopathy, CARP mRNA and protein levels were depleted, myofilament gene transcription was attenuated and sarcomeres showed significant disarray. In a transgenic mouse model of cardiac-specific overexpression of CARP, mice exhibited normal physiology at baseline, but were protected against pathological cardiac hypertrophy induced via pressure-overload or isoproterenol, which could be attributed to the downregulation of the ERK1/2, MEK and TGFbeta-1 pathways. Another study demonstrated that adenoviral overexpression of CARP in cardiomyocytes enhances cardiac hypertrophy induced by Angiotensin II or pressure-overload and promotes cardiomyocyte apoptosis via p53 activation and mitochondrial dysfunction. However, transgenic knockout models of either CARP alone or CARP in combination with the other muscle ankyrin repeat proteins (MARPs), ANKRD2 and ANKRD23 demonstrated a lack of cardiac phenotype; mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential. Interactions between CARP and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. Passive stretch in fetal cardiomyocytes induced differential CARP distribution at nuclei and I-band titin N2A regions. In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, CARP mRNA expression was shown to be 30-fold elevated in skeletal muscle tissue. Clinical significance A wide spectrum of clinical features have been associated with ANKRD1/CARP. Mutations in ANKRD1 have been associated with dilated cardiomyopathy, two of which result in altered binding with TLN1 and FHL2. Mutations in ANKRD1 have also been associated with hypertrophic cardiomyopathy, and have shown to increase binding of CARP to Titin and MYPN. Examination of the functional effects of CARP hypertrophic cardiomyopathy mutations in engineered heart tissue demonstrated that Thr123Met was a gain-of-function mutation exhibiting augmented contractile properties; whereas Pro52Ala and Ile280Val were unstable and failed to incorporate into sarcomeres, an effect that was remedied upon proteasome inhibition via epoxomicin. A missense mutation in ANKRD1 was shown to be associated with the congenital heart defect, Anomalous pulmonary venous connection. CARP has been found as a sensitive and specific biomarker for the differential diagnosis of rhabdomyosarcoma. ANKRD1 mRNA levels correlate with patient platinum sensitivity, thus ANKRD1 associates with platinum-based chemotherapy treatment outcome in ovarian adenocarcinoma patients. CARP and mRNA expression has been shown to