Skeletal and cardiac muscles are the only striated muscles in the body. Although sharing many structural and functional similarities, skeletal and cardiac muscles have intrinsic differences in terms of physiology and regenerative potential. While skeletal muscle possesses a robust regenerative response, the mammalian heart has limited repair capacity after birth. In this review, we provide an updated view regarding chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) function in vertebrate myogenesis, with particular emphasis on the skeletal and cardiac muscles. We also highlight the new insights of COUP-TFII hyperactivity underlying striated muscle dysfunction. Lastly, we discuss the challenges and strategies in translating COUP-TFII action for clinical intervention.
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