ORAI1 and hydrops fetalis: Secondly, as exemplified in channelopathy caused by GOF mutations in Orai1 resulting in constitutive or increased SOCE independent of STIM1 (Lacruz and Feske, 2015), therapeutic targeting of STIM1 might not be as efficient, taking into account that reduction of STIM1 might accelerate transition to HF (Benard et al., 2016).