PIP4K2C encodes a phosphatidylinositol-5-phosphate 4-kinase with unique regulatory properties in cellular metabolism and disease progression. The enzyme exhibits low enzymatic activity but functions as a GTP sensor with higher GTP-dependent than ATP-dependent kinase activity 1. PIP4K2C negatively regulates insulin signaling through a catalytic-independent mechanism by interacting with PIP5Ks and suppressing PIP5K-mediated PtdIns(4,5)P2 synthesis 1. Loss of PIP4K2C expression promotes liver metastasis by hypersensitizing cells to insulin-mediated PI3K/AKT signaling, allowing cancer cells to exploit the insulin-rich liver environment 2. The protein plays critical roles in autophagy regulation, with PIP4K2C inhibition reversing autophagic flux impairment induced by SARS-CoV-2 through binding to viral nonstructural protein 6 3. In cancer contexts, PIP4K2C expression correlates with poor prognosis - elevated levels promote breast cancer cell proliferation, migration, and invasion 4, while low PIP4K2C expression associates with favorable outcomes in acute myeloid leukemia 5. The enzyme also participates in alternative PtdIns(4,5)P2 synthesis pathways that distinguish cancer cell sensitivity to PIKFYVE inhibitors 6.