PI4K2A is a membrane-bound phosphatidylinositol 4-kinase that catalyzes phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a critical lipid second messenger precursor. The enzyme localizes to the trans-Golgi network, endosomes, lysosomes, and early endosome membranes, where it facilitates multiple cellular processes 1. PI4K2A functions in autophagosome-lysosome fusion through GABARAP binding via a conserved 7-amino acid motif in its catalytic domain 23. The enzyme plays essential roles in lysosomal repair following damage, where ATG9A-containing vesicles deliver PI4K2A to damaged lysosomes in cooperation with ARFIP2 1. In secretory/endocytic trafficking, epithelial-mesenchymal transition (EMT) activates a PI4KIIIβ-to-PI4K2A dependency switch that drives hypersecretion and metastatic phenotypes in lung cancer through MYOIIA-containing complexes and receptor recycling 4. PI4K2A also participates in non-canonical autophagy-mediated antitumor immunity by generating PI4P that recruits ATG12-Atg5-Atg16L1 complexes 5, and transfers inositol metabolic enzymes via extracellular vesicles to enhance homologous recombination repair in ovarian cancer 6. Clinically, PI4K2A mutations cause neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities 7, while elevated expression predicts poor prognosis in colon adenocarcinoma 8.