The present study aimed to investigate the potential regulation of the AA-dependent Orai3 influx by TNFα in early adaptive cardiac remodeling, identify the potential cellular source of such an inflammatory signal, evaluate the impact of TNFα-induced Orai3 regulation on cardiomyocyte hypertrophy and resistance to H2O2, and assess the functional relevance of Orai3 activity in HF. Here, ORAI3 is linked to hydrops fetalis.