Beyond ER-Golgi trafficking: unconventional protein secretion as a new design frontier for synthetic secretion switches in mammalian cells.

Unconventional protein secretion offers new design principles to enhance rapid control of extracellular protein release in mammalian cells.

• Why it matters: Current secretion switches rely on the classical ER-Golgi pathway, which limits response speed, host-cell flexibility, and cargo compatibility, hindering rapid and versatile extracellular responses.
• What they did: The authors review existing secretion-control architectures and explore unconventional protein secretion as an underutilized approach to position regulatory control closer to the final export step, broadening design options.
• The result: This perspective highlights how leveraging unconventional secretion mechanisms can enable faster, more adaptable, and less host-dependent protein release systems, advancing synthetic biology applications.