Abstract: Compositions and methods for modulating activity of store-operated calcium entry in cells or tissues are provided. The compositions comprise the P311 protein, fused to a cell-penetrating peptide and formulated for delivery to tissues and cells. This protein has been shown to increase the levels of store-operated calcium entry (SOCE) in gingival cells, skeletal muscle cells, and prostate epithelial cells. Also provided are methods for preventing and treating diseases that involve administration of the P311 fusion protein, as well as methods for increasing levels of SOCE in cells.