Models of the distribution of modes of action of Sac1 and of the distribution of ERTGoCS and PI4P among Golgi stacks. (A) Two possible modes of action of Sac1 at the ERTGoCS. The width of ERTGoCS ranges from 5 to 20 nm (Venditti et al., 2019). We envisage that the in-trans activity of Sac1 may occur only at the tighter contact sites and only when FAPP1 is present. In the cis mode, Sac1 acts on PI4P that is transferred from the TGN to the ER by OSBP1 in exchange for cholesterol. In this mode, Sac1 can also operate at contact sites that have a greater distance between the opposing membranes since OSBP1 can in principle shuttle between the TGN and the ER. (B) Two possible scenarios of ERTGoCS and PI4P distribution among Golgi stacks. I: The TGN of every Golgi stack can engage in ERTGoCS at any given time. PI4P levels are kept equal and at a medium level in the TGN of all the stacks. ApoB100 export also occurs from the TGN of every stack but at a low rate. II: Only TGN from a subset of Golgi stacks can engage in ERTGoCS. PI4P levels are heterogeneous in the TGN of different stacks, some with high levels of PI4P (devoid of ERTGoCS) and others with low PI4P levels. ApoB100 export occurs exclusively and at a high rate from a TGN with high PI4P levels.