Embedded in the Membrane: How Lipids Confer Activity and Specificity to Intramembrane Proteases.

Proteases, sharp yet unforgivable tools of every cell, require tight regulation to ensure specific non-aberrant cleavages. The relatively recent discovered class of intramembrane proteases has gained increasing interest due to their involvement in important signaling pathways linking them to diseases including Alzheimer's disease and cancer. Despite tremendous efforts, their regulatory mechanisms have only started to unravel. There is evidence that the membrane composition itself can regulate intramembrane protease activity and specificity. In this review, we highlight the work on γ-secretase and rhomboid proteases and summarize several studies as to how different lipids impact on enzymatic activity.