Myo-inositol-1,2,3,4,5,6-hexakisphosphate (InsP6), also known as phytic acid, accumulates in large quantities in plant seeds, serving as a phosphorus reservoir, but is an animal antinutrient and an important source of water pollution. Here we report that Gle1 (GLFG lethal 1) in conjunction with InsP6 functions as an activator of the ATPase/RNA helicase LOS4 (Low expression of osmotically responsive genes 4), which is involved in mRNA export in plants, supporting the Gle1-InsP6-Dbp5 (LOS4 homolog) paradigm proposed in yeast. Interestingly, plant Gle1 proteins have modifications in several key residues of the InsP6-binding pocket, which reduce the basicity of the surface charge. Arabidopsis Gle1 variants containing mutations that increase the basic charge of the InsP6-binding surface show increased sensitivity to InsP6 concentrations for the stimulation of LOS4 ATPase activity in vitro. Expression of the Gle1 variants with enhanced InsP6 sensitivity rescues the mRNA export defect of the ipk1 (inositol 1,3,4,5,6-pentakisphosphate 2-kinase) InsP6-deficient mutant, and furthermore, significantly improves vegetative growth, seed yield, and seed performance of the mutant. These results suggest that Gle1 is an important factor responsible for mediating InsP6 functions in plant growth and reproduction, and that Gle1 variants with increased InsP6 sensitivity may be useful for engineering high-yielding low-phytate crops.