Chasing the right tail: How the ER membrane complex recognizes its substrates.

Tail-anchored proteins are tethered to membranes of the ER, mitochondria, and peroxisomes. In this issue, Pleiner and colleagues (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202212007) show that the ER membrane complex (EMC) uses an inbuilt charge-dependent selectivity filter to specifically insert ER tail-anchored proteins according to their topology signals and to prevent the misincorporation of mitochondrial proteins.