IP6K1 (inositol hexakisphosphate kinase 1) catalyzes the phosphorylation of inositol hexakisphosphate (InsP6) to generate diphosphoinositol pentakisphosphate (5PP-InsP5/InsP7), a high-energy signaling molecule 1. This enzyme mediates diverse physiological processes through direct protein binding and serine pyrophosphorylation of target proteins 2. IP6K1 functions in metabolism, gene expression, DNA repair, and immunity 1. Mechanistically, IP6K1 regulates inositol biosynthesis by translocating to the nucleus upon phosphatidic acid binding, where it represses myo-inositol-3-P synthase expression 3. IP6K1 also forms protein complexes with substrate proteins and kinases like CK2 to coordinate substrate phosphorylation and pyrophosphorylation 2. Clinically, IP6K1 inhibition represents a therapeutic strategy for atherosclerosis: blocking IP6K1 increases apolipoprotein A-I production in hepatocytes by preventing its ubiquitin-mediated degradation, thereby enhancing cholesterol efflux and reducing atherosclerotic burden 4. Additionally, IP6K1 deletion protects against age-related metabolic dysfunction and improves insulin sensitivity by activating PKB/Akt and AMPK pathways 5. Conversely, IP6K1 upregulation mediates hyperglycemia-induced endothelial senescence by rewiring LKB1 signaling from AMPK toward p53 activation 6. Shared genetic loci containing IP6K1 show associations with depression and vitamin D levels, suggesting roles in neurodevelopment 7.