Bacterial lipoproteins are a specialised class of membrane proteins that represent a small percentage of the proteome of Gram-positive bacteria, yet these lipoproteins have been reported to play important roles in nutrient scavenging, cell envelope assembly, protein folding, environmental signalling, host cell adhesion and virulence. Upon translocation of lipoproteins, the type II signal peptidase (Lsp) cleaves the signal peptide, leaving the lipoproteins bound to the outer face of the cytoplasmic membrane by means of linking lipid molecule to their +1 cysteine residue. We have studied the role played by Lsp in Streptomyces lividans cellular metabolism, particularly, in secretory protein production, and found that the absence of functional Lsp, apparently produces a translocase blockage, diminishes the synthesis of secretory proteins and triggers a stringent response. These findings could be particularly relevant when optimising S. lividans for the overproduction of secretory proteins of industrial application.