Striated muscle cells form specialized junctional membrane complexes(JMCs)between the cell-surface transverse tubule and sarcoplasmic reticulum(SR)for setting up the excitation-contraction coupling machinery converting depolarization into Ca2+ release signals. Junctophilin subtypes, namely JP1-JP4, are proteins that construct JMCs by binding to the cell membrane and spanning the SR membrane. Recent studies demonstrated that the mutations and altered expression of JP2 take part in cardiac diseases. JPs dominantly affect Ca2+ signaling in striated muscle, and thus may be involved in pathogeneses and progressive pathophysiological conditions in a variety of muscle-related diseases.