ITPK1 is a multifunctional kinase/phosphatase that catalyzes the synthesis of inositol hexakisphosphate (InsP6), a critical signaling molecule. The enzyme phosphorylates inositol-1,3,4-trisphosphate (Ins(1,3,4)P3) and inositol-3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4) to generate inositol pentakisphosphate (IP5), which is further phosphorylated to InsP6 1. ITPK1 also possesses reversible phosphatase activity, allowing bidirectional conversion between IP5 and IP4, positioning it as a rate-limiting enzyme in the InsP6 pathway 2. Mechanistically, ITPK1 regulates calcium-activated chloride channel conductance through Ins(3,4,5,6)P4, which inhibits these channels essential for fluid secretion and cellular homeostasis 2. Clinically, ITPK1 dysfunction is implicated in multiple disease states. ITPK1 polymorphisms are associated with neural tube defects, particularly spina bifida, with reduced InsP6 concentrations and altered gene expression observed in carriers of risk alleles 34. Additionally, ITPK1 shows shared genetic associations with both migraine and thyroid dysfunction 5. Recent evidence indicates ITPK1 participates in insulin signaling-related cognitive decline in Alzheimer's disease, with lower ITPK1 levels moderating the association between AKT1 phosphorylation and cognitive deterioration 6. ITPK1 may regulate necroptotic and apoptotic cell death processes through highly phosphorylated inositol phosphates, representing a therapeutic target for diseases involving aberrant cell death.