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Here, we now have identified that the tail length of the C-terminal transmembrane domains (C-TMDs) determines efficient insertion and installation of membrane proteins into the ER. We discovered that membrane proteins with C-TMD tails smaller than ∼60 proteins are badly inserted into the ER membrane layer, which implies that interpretation is ended before they have been acquiesced by the Sec61 translocon for insertion. These C-TMDs with insufficient hydrophobic