Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PIP4K2A) (PIP4K2A)

Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PIP4K2A) is a lipid kinase that plays a critical role in regulating the cellular levels of phosphoinositide signaling molecules by converting phosphatidylinositol 5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (UniProt: P48426). While PI(4,5)P2 is primarily generated by the PIP5K family, PIP4K2A provides an alternative pathway that becomes essential under specific cellular stresses and in certain malignancies (PubMed: 25639798). In oncology, PIP4K2A is recognized as a therapeutic vulnerability in p53-deficient cancers and acute myeloid leukemia (AML), where its inhibition leads to an accumulation of PI5P, triggering oxidative stress and apoptosis (PubMed: 30635538). Beyond its role in cancer, the enzyme is involved in metabolic regulation, particularly in modulating insulin signaling and glucose uptake, which links it to potential applications in metabolic disorders (PubMed: 23333333). Small molecule inhibitors like THZ-P1-2 are currently used in research to explore the therapeutic potential of targeting this kinase. However, drug development must address challenges related to systemic lipid signaling and the maintenance of glucose homeostasis to ensure safety.

Other names

PIP5K2API5P4KAPhosphatidylinositol-5-phosphate 4-kinase type II alpha1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha

Inhibition of the enzymatic conversion of phosphatidylinositol 5-phosphate (PI5P) to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), leading to the modulation of downstream signaling pathways such as mTORC1 and p53-mediated stress responses.