PIP4K2A

PIP4K2A encodes phosphatidylinositol-5-phosphate 4-kinase α (PI5P4Kα), a type II phosphoinositide kinase that phosphorylates phosphatidylinositol-5-phosphate (PI5P) to generate phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂), a key signaling lipid that supports phosphoinositide-dependent cellular regulation and membrane-associated signaling processes^[1][2]. Mechanistically, PI5P4Kα contributes to intracellular phosphoinositide homeostasis and has been linked to autophagy regulation, nutrient-stress responses, and metabolic control through coordination of organelle-associated signaling networks^[3][4]. These functions have attracted substantial interest in cancer biology, where genetic or pharmacological disruption of PI5P4K family members has been associated with altered cellular metabolism, impaired autophagic flux, and reduced proliferation in selected tumor models, particularly those with defects in TP53 signaling^[5][6]. Compared with related isoforms, PIP4K2A, PIP4K2B, and PIP4K2C encode PI5P4Kα, PI5P4Kβ, and PI5P4Kγ, respectively, but the isoforms display distinct enzymatic activities, with PI5P4Kα exhibiting the highest catalytic activity and PI5P4Kγ showing markedly lower activity in biochemical assays^[7]. For experimental applications, PI5P4Kα has become a tractable pharmacological target, and both the covalent pan-PI5P4K inhibitor THZ-P1-2 and the highly selective PIP4K2A inhibitors BAY-091 and BAY-297 are widely used as chemical probes to investigate PI5P4K signaling, autophagy, cancer metabolism, and isoform-specific biological functions^[5][8][9].