The YebST system (renamed the LetAB system) of intermembrane phospholipid translocation (Nakayama and Zhang-Akiyama 2016). LetA is a 427 aa protein with 8 TMSs in the cytoplasmic membrane while LetB  is an 877 aa protein; it spans the periplasm and has an N-terminal TMS followed by seven repeats that are stacked on top of each other to form a channel across the periplasm. The first repeat accepts the phospholipid from LetA while the seventh repeat interacts with the outer membrane where it delivers the phospholipid (Isom et al. 2020).  Santarossa et al. 2025 determined the structure of E. coli LetAB, a phospholipid transporter involved in outer membrane integrity, and found that LetA adopts a distinct architecture that is structurally and evolutionarily unrelated to known transporter families. LetA functions as a pump at one end of a ~225 Å long tunnel formed by its binding partner, MCE protein LetB, creating a pathway for lipid transport between the inner and outer membranes. Unexpectedly, the LetA transmembrane domains adopt a fold that is evolutionarily related to the eukaryotic tetraspanin family of membrane proteins, including TARPs and claudins. LetA has no detectable homology to known transport proteins, and defines a new class of membrane transporters. Through a combination of deep mutational scanning, molecular dynamics simulations, AlphaFold-predicted alternative states, and functional studies, Santarossa et al. 2025 presented a model for how the LetA-like family of membrane transporters may use energy from the proton-motive force to drive the transport of lipids across the bacterial cell envelope.