PI4KA encodes phosphatidylinositol 4-kinase alpha, an essential lipid kinase that serves as a master regulator of phosphoinositide signaling at the plasma membrane 1. PI4KA produces the predominant pool of phosphatidylinositol 4-phosphate (PI4P) at the plasma membrane, which is crucial for lipid transport and regulation of PLC and PI3K signaling pathways 1. The enzyme functions as a heterotrimeric complex with regulatory proteins TTC7 and FAM126, and is recruited to the plasma membrane by EFR3 proteins 2. PI4KA undergoes multiple levels of regulation, including posttranslational modifications and interaction with calcineurin phosphatase, which dephosphorylates and promotes PI4KA complex activity during signaling 3. Biallelic PI4KA mutations cause severe multisystem disorders including gastrointestinal defects, immunodeficiency, and neurodevelopmental abnormalities 4. These mutations disrupt B-cell metabolism by altering lipid production, impairing mitochondrial function, and hyperactivating the mTOR pathway, resulting in B-cell lymphopenia and hypogammaglobulinemia 4. Clinical manifestations include spastic paraplegia, hypomyelinating leukodystrophy, developmental delay, and recurrent infections 56. The enzyme's conservation across all eukaryotes underscores its fundamental importance in cellular membrane organization and signaling 1.