{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPI4KB is a type III phosphatidylinositol 4‑kinase that catalyzes the phosphorylation of phosphatidylinositol (PI) to generate phosphatidylinositol 4‑phosphate (PI4P), a pivotal lipid that defines Golgi membrane identity and governs vesicular trafficking. Its enzymatic activity is tightly regulated by interactions with specific proteins such as the Golgi adaptor ACBD3 and 14‑3‑3 factors that not only aid in membrane recruitment but also protect PI4KB from proteolytic degradation, ensuring localized PI4P synthesis within discrete subdomains of the Golgi complex. These structural and biochemical insights underscore a central role for PI4KB in linking lipid signaling to membrane dynamics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPI4KB has emerged as a critical host factor for the replication of numerous RNA viruses. In hepatitis C virus (HCV) infection, for example, modulation of PI4KB via host factors—and its interaction with viral proteins such as NS5A—leads to the formation of PI4P‑rich replication sites. In picornavirus infections, including enteroviruses and Aichi virus, viral 3A proteins and associated factors like ACBD3 hijack PI4KB to remodel Golgi membranes into replication organelles, thereby optimizing the lipid environment for viral genome replication. Additionally, studies indicate that while inhibition or knockdown of PI4KB markedly reduces replication for diverse genotypes of HCV and enteroviruses, certain viruses like foot‐and‐mouth disease virus bypass the dependency on PI4KB. Emerging evidence further implicates PI4KB in the replication of negative‑strand viruses such as human parainfluenza virus type 3, as well as in infections caused by EV71, underscoring its broad involvement in viral lifecycle regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in viral propagation, PI4KB is integral to several cellular signaling and trafficking processes. It facilitates ceramide transport from the endoplasmic reticulum to the Golgi—thereby influencing sphingomyelin synthesis—and is activated by factors such as eEF1A2 to modulate actin dynamics, which in turn can lead to filopodia formation and altered acinar morphogenesis in breast epithelial cells. Furthermore, in cardiomyocytes PI4KB has been implicated in the regulation of glucose transporter (GLUT4) vesicle trafficking, thereby promoting insulin-independent glucose uptake and impacting cellular energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe precise localization and multifaceted functions of PI4KB are orchestrated by its recruitment to Golgi membranes through its interaction with ACBD3 and other adaptor proteins. This recruitment not only ensures the spatially restricted generation of PI4P but also integrates PI4KB activity into broader regulatory networks that impact membrane trafficking, signal transduction, and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin Klima, Dániel J Tóth, Rozalie Hexnerova, et al. 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