Phosphatidylinositol 4-kinase IIα (PI4K IIα) is one of the four mammalian lipid kinases that catalyse the conversion of phosphatidylinositol to phosphatidylinositol 4 phosphate, a major precursor of higher phosphoinositides and a key lipid molecule in a receptor-mediated signalling pathway [1]. Since PI4K IIa is a constitutively membrane bound protein, its enzymatic activity is modulated indirectly via changing the lipid composition and affecting the enzyme diffusion in a phospholipid bilayer [2]. The functional role of PI4K IIα in a cell physiology is still not fully understood. Here, we present the crystal structure of human PI4K IIα in complex with ATP [3]. The structure revealed a bi-lobal character (N- and C-lobes) of the catalytic domain with the ATP binding pocket positioned in between. Furthermore, a unique lateral hydrophobic pocket with a second ATP bound was found in the C-lobe of the catalytic domain. Molecular dynamic simulations and mutagenesis analysis revealed the membrane binding mode and a putative function of a lateral hydrophobic pocket. Altogether, these results provided the insight into a functional state of PI4IIα when bound to the membrane.