Abstract: We have investigated the role of CseA in the sigma(E) cell envelope stress response of the gram-positive bacterium Streptomyces coelicolor. sigma(E) is an extracytoplasmic function RNA polymerase sigma factor required for normal cell envelope integrity in S. coelicolor. sigma(E) is encoded within a four-gene operon that also encodes CseA, a protein of unknown function, CseB, a response regulator and CseC, a transmembrane sensor histidine kinase (Cse represents control of sigma E). Previous work has shown that transcription of the sigE gene is completely dependent on the CseBC two-component system and that the CseBC-sigma(E) signal transduction system is induced by a wide variety of cell-wall-damaging agents. Here we address the role of CseA, a protein with no homologues outside the streptomycetes. We show that CseA is a novel lipoprotein localized to the extracytoplasmic face of the cell membrane and that loss of CseA results in upregulation of the sigE promoter.