Mechanisms and cellular functions of intramembrane proteases

Siniša Urban

Research output: Contribution to journalEditorialpeer-review

15 Scopus citations


The turn of the millennium coincided with the branding of a fundamentally different class of enzyme - proteases that reside immersed inside the membrane. This new field was the convergence of completely separate lines of research focused on cholesterol homeostasis, Alzheimer's disease, and developmental genetics. None intended their ultimate path, but soon became a richly-integrated fabric for an entirely new field: regulated intramembrane proteolysis. Our aim in this Special Issue is to focus on the ancient and nearly ubiquitous enzymes that catalyze this unexpected yet important reaction. The pace of progress has been dramatic, resulting in a rapidly-expanding universe of known cellular functions, and a paradigm shift in the biochemical understanding of these once heretical enzymes. More recently, the first therapeutic successes have been attained by targeting an intramembrane protease. We consider these advances and identify oncoming opportunities in four parts: growing spectra of cellular roles, insights into biochemical mechanisms, therapeutic strategies, and newly-emerging topics. Recent studies also expose challenges for the future, including non-linear relationships between substrate identification and physiological functions, and the need for potent and specific, not broad-class, inhibitors.

Original languageEnglish (US)
Pages (from-to)2797-2800
Number of pages4
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number12
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology


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