Working model for the facilitation of CARTS biogenesis by the SCAP–SREBP complex at ER–Golgi MCSs. Low cholesterol (Chol) levels: SCAP escorts SREBP transcription factors from the ER to the Golgi complex for cholesterol synthesis and uptake (left panel, blue arrows). Sufficient cholesterol levels: a complex of cholesterol-bound SCAP and SREBP interacts with the VAP–OSBP complex via Sac1 and functions in the counter-transport of ER cholesterol and Golgi PI4P at ER–Golgi MCSs to promote CARTS biogenesis at the TGN domains immediately adjacent to the ER MSCs (left panel, red arrows, and right panel). PC, phosphatidylcholine.