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Skeletal muscle consists of type I and type II myofibers, which exhibit different metabolic and contractile properties. Type I fibers display an oxidative metabolism and are resistant to fatigue, whereas type II fibers are primarily glycolytic and suited for rapid bursts of activity. These properties can be modified by changes in workload, activity, and hormonal stimuli, facilitating muscle adaptation to physiological demand. The MEF2 transcription factor promotes the formation of slow-twitch (type I) muscle fibers in response to activity. MEF2 activity is repressed by class II histone deacetylases (HDACs) and is enhanced by calcium-regulated protein kinases that promote the export of class II HDACs from the nucleus to the cytoplasm. However, the identities of skeletal muscle class II HDAC kinases are not well defined. Here we demonstrate that protein kinase D1 (PKD1), a highly effective class II HDAC kinase, is predominantly …