Regulation and function of PI4P at the Golgi complex

Fifty years after Bob Michell's visionary prediction, phosphatidylinositol 4-phosphate (PI4P) has emerged as a central regulator of Golgi function, influencing membrane trafficking, lipid metabolism, and signaling. PI4P homeostasis is tightly controlled by phosphatidylinositol 4-kinases (PI4Ks), phosphatidylinositol transfer proteins (PITPs), and the phosphatase SAC1, ensuring precise regulation across Golgi subdomains. Beyond its classical role in vesicular transport, PI4P orchestrates lipid exchange at membrane contact sites, enabling dynamic Golgi maturation and functional specialization. The interplay between PI4P, lipid transfer proteins, and Golgi adaptors underlies cargo sorting, glycosylation, and organelle architecture. Emerging evidence also highlights PI4P's role in oncogenesis and cellular signaling, positioning the Golgi as a critical hub beyond secretion. Yet, key questions remain regarding PI4P compartmentalization and its broader physiological impact. This review revisits PI4P's essential functions, integrating historical insights with recent discoveries to illuminate its pivotal role in Golgi biology and beyond.