be rapidly altered by post-translational mechanisms. Functional insights into ARPP function have come from transgenic studies. In mice lacking all three muscle ankyrin repeat proteins (MARPs), ARPP, CARP, and DARP), skeletal muscles tended towards a more slower fiber type distribution, with longer resting sarcomere length, decreased fiber stiffness, expression of a longer titin isoform, greater degree of torque loss following eccentric contraction-related injury, and enhanced expression of MyoD and MLP. These findings suggest that ARPP and related MARP proteins may play a role in the passive stiffness and gene regulatory roles in skeletal muscle. A study investigating ARPP function in cardiac muscle in which ARPP was knocked out alone or in combination with the other MARPs showed that mice displayed normal cardiac function at baseline and in response to pressure overload-induced cardiac hypertrophy, suggesting that these proteins are not essential for normal cardiac development or in response to a hypertrophic stimulus. ARPP has also shown to play a role in models of disease. ARPP has also exhibited elevated expression following skeletal muscle denervation, persisting for four weeks following the insult. ARPP (ANKRD2) gene expression was also shown to be rapidly induced in a model of eccentric contraction-related injury, showing peak expression (6-11 times normal value) within 12–24 hours following injury, suggesting that ARPP may play a role in repair. In a mouse model of muscular dystrophy with myositis (mdm) caused by a small deletion in titin, ANKRD2 mRNA expression was shown to be significantly elevated in skeletal muscle tissue along with that of CARP, suggesting a role for ARPP in titin-based signaling. Levels of ARPP were also altered in a mouse model of diabetes. Clinical Significance In patients with dilated cardiomyopathy, levels of ARPP were upregulated. ARPP expression patterns have been shown to be altered in patients with amyotrophic lateral sclerosis (ALS), with decreased expression in slow skeletal muscle fibers and increased expression in fast skeletal muscle fibers. ARPP has also been shown to be a potentially useful biomarker for the differential diagnosis between oncocytoma and chromophobe renal cell carcinomas. In non-pathologic physiology, ARPP mRNA expression in skeletal muscle of patients was shown to be elevated two days following fatiguing jumping exercises. Levels of CARP, MLP and calpain-2 mRNA levels were also enhanced, suggesting that these molecules may be part of a signaling network activated by physical exercise. Ankrd2 has been shown to be involved in the progression of some