Aims: Ca²⁺ entry into mast cells is critically important for the antigen-induced stimulation of degranulation via the FcRI receptor. The Ca²⁺ entry is accomplished by the store operated, calcium release-activated calcium current (I_CRAC). Most recently, mast cell I_CRAC has been shown to critically depend on the serum- and glucocorticoid-inducible kinase 1 (SGK1). The purpose of the study was to investigate if and how SGK1 regulates I_CRAC. Methods: Bone marrow derived mast cells (BMMCs) were isolated from SGK1 knockout mice (sgk1^-/-) and their wild-type littermates (sgk1^+/+). Orai1 protein abundance in the cell membrane was determined by confocal microscopy and western blotting. In addition, the influence of SGK1 on store-operated calcium entry (I_CRAC) was investigated by Fura 2 fluorescence in BMMCs and human embryonic kidney (HEK293) cells stably expressing Orai1 and transfected with STIM1 and/or SGK1. Furthermore, I_CRAC was directly measured using patch clamp. Finally, Xenopus oocytes were used to investigate the mechanism between SGK1 and I_CRAC. Results: I_CRAC in Orai1 expressing HEK cells was significantly enhanced by additional expression of STIM1 and further enhanced by additional expression of constitutively active ^S422DSGK1. Additional expression of inactive ^K127NSGK1 significantly decreased I_CRAC in Orai1/STIM1 expressing HEK cells. In sgk1^+/+ mice BMMCs cell membrane Orai1 protein abundance was significantly higher than in sgk1^-/- BMMCs. Accordingly, I_CRAC was significantly larger in sgk1^+/+ BMMCs than in sgk1^-/- BMMCs. Conclusions: The results demonstrate that SGK1 plays an important role in the regulation of STIM1 and Orai1.