Unconventional protein secretion - new insights into the pathogenesis and therapeutic targets of human diseases

Jiyoon Kim, Heon Yung Gee, Min Goo Lee

Research output: Contribution to journalReview articlepeer-review

59 Citations (Scopus)


Most secretory proteins travel through a well-documented conventional secretion pathway involving the endoplasmic reticulum (ER) and the Golgi complex. However, recently, it has been shown that a significant number of proteins reach the plasma membrane or extracellular space via unconventional routes. Unconventional protein secretion (UPS) can be divided into two types: (i) the extracellular secretion of cytosolic proteins that do not bear a signal peptide (i.e. leaderless proteins) and (ii) the cell-surface trafficking of signal-peptide-containing transmembrane proteins via a route that bypasses the Golgi. Understanding the UPS pathways is not only important for elucidating the mechanisms of intracellular trafficking pathways but also has important ramifications for human health, because many of the proteins that are unconventionally secreted by mammalian cells and microorganisms are associated with human diseases, ranging from common inflammatory diseases to the lethal genetic disease of cystic fibrosis. Therefore, it is timely and appropriate to summarize and analyze the mechanisms of UPS involvement in disease pathogenesis, as they may be of use for the development of new therapeutic approaches. In this Review, we discuss the intracellular trafficking pathways of UPS cargos, particularly those related to human diseases. We also outline the disease mechanisms and the therapeutic potentials of new strategies for treating UPS-associated diseases.

Original languageEnglish
Article numberjcs213686
JournalJournal of cell science
Issue number12
Publication statusPublished - 2018 Jun 1

Bibliographical note

Funding Information:
We thank Dong Soo Chang for the assistance with illustrations. This work was supported by grant 2013R1A3A2042197 from the National Research Foundation, the Ministry of Science, ICT & Future Planning, Republic of Korea, and grant HI15C1543 of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea.

Publisher Copyright:
© 2018. Published by The Company of Biologists Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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