Updated project metadata. The locus of heat resistance (LHR) confers extreme heat resistance in E. coli. This study explored the role of the LHR in pressure resistance of E. coli, as well as its relationship with protein folding and aggregation in vivo. The role of LHR was investigated in E. coli MG1655 expressing a ibpA-yfp fusion. The expression of proteins by the LHR was determined by mass spectrometry based proteomics; inclusion bodies of untreated and treated cells were also analysed by proteomics, and by observation with fluorescence microscope. In total, 11 proteins of LHR were expressed, including sHSP20, ClpKGI, sHSP, YdfX1 and YdfX2, HdeD, KefB, Trx, PsiE, DegP, and a hypothetical proteins. The proteomic analysis of inclusion bodies revealed a differential abundance of proteins related to oxidative stress in strains carrying the LHR. The LHR reduced the presence of inclusion bodies after heat or pressure treatment, indicating that proteins expressed by the LHR prevent or reverse protein aggregation. The phenotype of the LHR was also mediated by the expression of a fragment containing only sHSP20, ClpKGI, sHSP. The LHR and the fragment encoding only for sHSP20, ClpKGI, sHSP also enhanced pressure resistance in E. coli MG1655 but had no effect on pressure resistance of E. coli LMM1010. In conclusion, the LHR confers pressure resistance to some strains of E. coli, and reduces protein aggregation. Pressure and heat resistance, however, are also dependent on additional LHR-encoded functions.