['Xin is a striated muscle-specific F-actin binding protein that has been implicated in cardiomyopathies. In cardiomyocytes, Xin is localized at intercalated discs (IDs). Mice lacking only two of the three Xin isoforms (XinAB(-/-) mice) develop severe cardiac hypertrophy. To further investigate the function of Xin variants in the mammalian heart, we generated XinABC(-/-) mice deficient in all Xin isoforms.', 'XinABC(-/-) mice showed a very mild phenotype: heart weight, heart weight to tibia length ratios, and cardiac dimensions were not altered. Increased perivascular fibrosis was only observed in hearts of young XinABC(-/-) mice. Striking differences were revealed in isolated cardiomyocytes: XinABC(-/-) cells demonstrated a significantly increased number of non-terminally localized ID-like structures. Furthermore, resting sarcomere length was increased, sarcomere shortening, peak shortening at 0.5-1 Hz, and the duration of shortening were decreased, and shortening and relengthening velocities were accelerated at frequencies above 4 Hz in XinABC(-/-) cardiomyocytes. ECG showed a significantly shorter HV interval and a trend towards shorter QRS interval in XinABC(-/-) mice, suggesting a faster conduction velocity of the ventricular-specific conduction system. In human cardiac tissue, expression of XinC protein was detected solely in samples from patients with cardiac hypertrophy.'] Does complete loss of murine Xin result in a mild cardiac phenotype with altered distribution of intercalated discs?