PI4K2A is a membrane-bound phosphatidylinositol 4-kinase that catalyzes phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid essential for endocytosis, Golgi function, protein sorting, and membrane trafficking. PI4P also serves as the first committed precursor in generating phosphatidylinositol 4,5-bisphosphate (PIP2) and inositol 1,4,5-trisphosphate (InsP3). PI4K2A localizes to the trans-Golgi network, endosomes, and early endosomes, where it regulates autophagosome-lysosome fusion through GABARAP binding and controls lysosomal repair in response to damage 1. PI4K2A deficiency causes developmental and epileptic-dyskinetic encephalopathy, presenting with corpus callosum dysgenesis, white matter loss, and hypoplastic vermis 2. The gene has also been identified as a cause of early-onset dystonia 3. In cancer, PI4K2A promotes tumor progression through multiple mechanisms: epithelial-mesenchymal transition (EMT) drives PI4K2A-dependent secretory and endocytic vesicular trafficking in lung cancer, establishing a hypersecretory state that facilitates metastasis 4; PI4K2A-derived extracellular vesicles mediate transfer of inositol metabolic enzymes to enhance homologous recombination repair in ovarian cancer, and targeting this pathway with fluoxetine (a selective serotonin reuptake inhibitor) sensitizes tumors to cisplatin and PARP inhibitors 5; high PI4K2A expression predicts poor prognosis and immunotherapy resistance in colon adenocarcinoma 6. PI4K2A also participates in antitumor immunity by generating PI4P that recruits autophagy machinery for intercellular transfer of activated STING 7.