(A) Phosphatidylinositol-4-phosphate (PI4P) is the Golgi membrane insertion site for Golgi phosphoprotein 3 (GOLPH3), a pivotal regulator of Golgi membrane dynamics and vesicle biogenesis. Golgi PI4P is generated by two Golgi-localized phosphatidylinositol 4-kinases (PI4Ks): PI4KIIIβ and PI4KIIα. PI4K antagonists block PI4P synthesis and impair secretion. (B) Golgi scaffold GOLIM4 recruits effectors of vesicle biogenesis (GOLPH3) and cargo sorting (ATP2C1) to activate secretion. GOLIM4 is degraded by manganese (Mn), resulting in diminished secretion. (C) P53 loss increased the expression levels of the Golgi scaffold GRASP55. GOLGIN45 is a client of GRASP55 and generates a protein complex that promotes vesicle biogenesis. GRASPIN disrupts the interaction between GRASP55 and GOLGIN45. (D) The Golgi scaffold PAQR11 is induced upon the loss of P53. PAQR11 promotes the secretion of PLAU, which functions in an autocrine manner by binding to the PLAU receptor (PLAUR). Activated PLAUR, in turn, promotes the expression of PAQR11. PLAUR inhibitor (PLAURi) prevents the binding of secreted PLAU to PLAUR, effectively terminating an autocrine signaling pathway that drives secretion.