Cardiac maturation is an important developmental phase where there are profound biological and functional changes after birth in mammals. Herein, we use our profiling of human heart maturation in vivo to identify key drivers of maturation in our human cardiac organoid (hCO) model. In this dataset, we exemplified the applicability of our mature organoids in modelling cardiac contraction. Three calsequesterin-2 (CASQ2) knock out (-/-) hCO lines were generated to demonstrate the effect of sarcoplasmic reticulum Ca2+ leakiness on contraction. In this dataset, we evaluate the proteomic remodelling induced by CASQ2 (-/-, n=3) versus CTRL mature hCOs (n=1).