Phosphatidylinositol 4-kinase type 2-alpha (PI4K2A)

Phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) is a membrane-bound lipid kinase and the most abundant phosphatidylinositol 4-kinase in human cells, catalyzing the formation of phosphatidylinositol 4-phosphate (PI4P) from phosphatidylinositol[1][4]. PI4P is a precursor for other phosphoinositides critical for cellular signaling and membrane trafficking, particularly in the Golgi apparatus and endosomal systems[1][4]. PI4K2A is palmitoylated for membrane association and is involved in processes such as endosomal sorting, targeting of clathrin adaptor complexes, and regulating key signaling pathways (including EGFR and Wnt)[1][2]. It is also essential for lysosomal repair, rapidly producing PI4P at damaged lysosomal membranes and facilitating endoplasmic reticulum-lysosome lipid transfer and contact formation[1]. Mutations and dysfunction in PI4K2A have been linked to neurodegenerative syndromes, developmental disorders, cancer, and lysosomal storage diseases[1][4]. Its molecular structure includes a unique non-typical kinase fold and a membrane-facing hydrophobic pocket, potentially involved in allosteric regulation[5]. No approved drugs specifically target PI4K2A directly, and clinically relevant inhibitors or biomarkers for patient selection have not been established in the current literature[4]. Safety concerns center around the enzyme's essential roles; its loss or inhibition is associated with severe pathology, especially neurodegeneration and lysosome dysfunction[1][4].

Other names

Phosphatidylinositol 4-kinase type II-alphaPI4KIIPhosphatidylinositol 4-kinase II-alphaPI4K2-alphaDKFZP761G1923PIK42ANEDMSB

Inhibition of kinase activity (general for kinase inhibitors; no specific drugs are identified in the available sources)