Mechanism of excitation-contraction (EC) coupling in immature hearts are considered to be different from those in the adults because of the structural immaturity of the sarcoplasmic reticulum (SR), an intracellular Ca²⁺ store, and the different expression of Ca²⁺-regulatory proteins. However, the detailed molecular mechanism is not completely understood. In the present study, we identified neuronal Ca²⁺ sensor-1 (NCS-1), an EF-hand Ca²⁺ binding protein that is important for neuronal functions, also functions as a novel regulator of EC coupling in young hearts. We found that NCS-1 is highly expressed in immature hearts, and its deletion decreased their contractile functions. NCS-1 enhances Ca²⁺ signals mainly by promoting the IP₃ receptor functions, followed by CaMKII signaling, which results in a large increase in the SR Ca²⁺ content that enhances SR-dependent EC coupling. In addition, NCS-1 expression increases in the early stages of hypertrophy and promotes progression of hypertrophy at least in part through IP₃R-dependent elevation of nuclear Ca²⁺ signaling. Our results reveal a previously unrecognized mechanism of EC coupling in young heart and the progression of cardiac hypertrophy. We propose that the proteins involved in NCS-1-mediating Ca²⁺ signaling can be novel therapeutic targets for cardiac diseases in immature hearts.