PIP5K1A is a lipid kinase that catalyzes phosphorylation of phosphatidylinositol 4-phosphate to generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical second messenger regulating signal transduction, vesicle trafficking, actin cytoskeleton dynamics, and cell adhesion 1. PIP2 serves as substrate for generating downstream signaling molecules including IP3, DAG, and PIP3 1. Beyond its canonical catalytic role, PIP5K1A functions through kinase-independent mechanisms: it regulates let-7 miRNA biogenesis by interacting with nuclear export protein XPO5 in nuclear speckles 2, and controls cell migration through RAC1 translocation to the plasma membrane 3. Clinically, PIP5K1A dysregulation drives multiple cancers through distinct mechanisms. In glioblastoma, PIP5K1A activates PI3K/AKT/MYC signaling downstream of β2-microglobulin, promoting stem cell maintenance 4. In hepatocellular carcinoma, PIP5K1A suppresses ferroptosis by stabilizing NRF2 through kinase-independent binding to KEAP1, conferring sorafenib resistance 5. Circular RNA PIP5K1A promotes cisplatin resistance in ovarian and lung cancers via miRNA sponging mechanisms 6, 7. In colorectal cancer, PIP5K1A promotes proliferation through Akt/CDK2 pathway activation 3. PIP5K1A represents an emerging therapeutic target across multiple malignancies.