JSRP1 encodes JP-45, an integral protein of the junctional sarcoplasmic reticulum membrane that plays a critical role in skeletal muscle excitation-contraction coupling (ECC) 1. JP-45 directly interacts with the voltage-sensitive calcium channel Cav1.1 (CACNA1S) through its cytoplasmic domain (residues 1-80), specifically binding to the I-II loop and C-terminal region of Cav1.1 1. This interaction is functionally significant, as JP-45 regulates Cav1.1 membrane targeting and activity - overexpression decreases peak charge movement and shifts voltage sensitivity, while depletion reduces Cav1.1 content and charge movements 1. Two common population variants (P108L and G150A) have been identified that decrease DHPR sensitivity to activation, potentially affecting ECC coupling efficiency 2. These variants are equally distributed among malignant hyperthermia susceptible and non-susceptible individuals, suggesting they may modulate phenotypic expression of RYR1 mutations 2. JP-45 expression changes with aging, contributing to excitation-contraction uncoupling in elderly skeletal muscle 3. The protein also interacts with calsequestrin and colocalizes with ryanodine receptors at the junctional face membrane, positioning it as a key regulator of calcium homeostasis in skeletal muscle 1.