Signal Peptides and Their Fragments in Post-Translation: Novel Insights of Signal Peptides

Signal peptides (SPs), peptide sequences located at the N-terminus of newly synthesized proteins, are primarily known for their role in targeting proteins to the endoplasmic reticulum (ER). It has traditionally been assumed that cleaved SPs are rapidly degraded and digested near the ER. However, recent evidence has demonstrated that cleaved SP fragments can be detected in extracellular fluids such as blood flow, where they exhibit bioactivity. In addition, SP fragments are delivered to extracellular fluids via extracellular vesicles such as exosomes and microvesicles, which are important mediators of intercellular communication. These findings suggest that SPs and their fragments may have physiological roles beyond their classical function. This review aims to provide a comprehensive overview of these novel roles and offer new insights into the potential functions of SPs and their fragments in post-translational regulation and intercellular communication.