TolC is an outer-membrane protein that serves as an activated exit duct in multi-drug efflux pumps and protein secretion machinery. We have discovered that the E. coli lipoprotein YbjP interacts extensively with the periplasmic surface of TolC and its N-terminal lipid moiety is embedded in the membrane, mimicking the intramolecular and modification-membrane interactions seen in TolC homologs. Our results suggest that YbjP may contribute to stabilising the orientation and distribution of TolC in the outer membrane as well as the expression of transporters. The accompanying data corresponds to DIA mass spectra from tolC, ybjP, tolC-ybjP mutants, as well as WT E. coli as a reference.