Inositol hexakisphosphate kinase 1 (IP6K1)

Inositol hexakisphosphate kinase 1 (IP6K1) is a member of the inositol phosphokinase family of enzymes responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (5-IP7), a molecule with high energy phosphate bonds that is involved in a wide range of cellular signaling functions. IP6K1 is central to phosphate homeostasis, cellular energy metabolism, and inositol pyrophosphate synthesis in mammalian cells. It regulates several cellular processes including actin cytoskeleton dynamics, focal adhesion, microtubule trafficking, cell migration, angiogenesis, bone integrity, insulin secretion, and stem cell fitness. In addition to its metabolic roles, IP6K1 modulates mRNA translation repression and processing body formation via binding to translation initiation factors and mRNA decapping complexes. It also acts as a negative regulator of inositol synthesis through epigenetic mechanisms including DNA and histone methylation. IP6K1 is implicated in the pathophysiology of cancer, metabolic disease (obesity, type 2 diabetes, osteoporosis), kidney disease, and infection, making it an increasingly attractive therapeutic target. However, due to its widespread roles, inhibition must be carefully controlled to avoid unwanted effects on immunity, tumor progression, and development.

Other names

Inositol hexakisphosphate kinase 1IP6K1IHPK1KIAA0263InsP6 kinase 1PiUSATP:1D-myo-inositol-hexakisphosphate phosphotransferasePi uptake stimulatorinositol hexaphosphate kinase 1insP6 kinase 1

Inhibition of IP6K1 decreases 5-IP7 (inositol pyrophosphate) synthesis, thereby affecting cellular phosphate export, energy metabolism, and ATP concentration. Pharmacological inhibition modulates neutrophil and platelet activity reducing harmful inflammation during infection. Alters insulin secretion and sensitivity by affecting ATP/ADP ratio in β-cells.