Phosphatidylinositol 5-phosphate 4-kinase type 2 alpha (PI5P4Kα) (PI5P4Kα)

Phosphatidylinositol 5-phosphate 4-kinase type 2 alpha (PI5P4Kα), encoded by the PIP4K2A gene, is a lipid kinase that plays a critical role in regulating the levels of phosphoinositides, specifically 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 PI4P 5-kinases, the PI5P4K family provides an alternative pathway that is particularly important under stress conditions or in specific cellular compartments like the nucleus [PMID: 23333311]. PI5P4Kα is frequently overexpressed in various cancers, including breast cancer and acute myeloid leukemia, where it supports cell survival and proliferation, often in a TP53-dependent manner [PMID: 30842659]. In the context of metabolism, it acts as a negative regulator of insulin signaling, making it a potential target for metabolic disorders [PMID: 12618914]. Therapeutic strategies focus on small-molecule inhibitors that disrupt its kinase activity to induce metabolic stress and apoptosis in cancer cells [PMID: 26711006]. However, the high structural similarity between the alpha, beta, and gamma isoforms poses a challenge for achieving isoform-specific inhibition [PMID: 26711006].

Other names

PIP4K2APIP4KIIAPIP5K2APhosphatidylinositol 5-phosphate 4-kinase type II alpha

Small-molecule inhibition of the kinase domain to prevent the conversion of PI5P to PI(4,5)P2, leading to increased PI5P levels and subsequent induction of ROS-mediated apoptosis or growth arrest in cancer cells [PMID: 26711006, 30842659].