Nature Reviews Molecular Cell Biology 13, 489-498 (August 2012) | doi:10.1038/nrm3392

New lives for old: evolution of pseudoenzyme function illustrated by iRhoms

Colin Adrain1 & Matthew Freeman1  About the authors


Large-scale sequencing of genomes has revealed that most enzyme families include inactive homologues. These pseudoenzymes are often well conserved, implying a selective pressure to retain them during evolution, and therefore that they have significant function. Mechanistic insights and evolutionary lessons are now emerging from the study of a broad range of such 'dead' enzymes. The recently discovered iRhoms — inactive homologues of rhomboid proteases — have joined derlins and other members of the rhomboid-like clan in regulating the fate of proteins as they pass through the secretory pathway. There is a strong case that dead enzymes, which have been rather overlooked, may be a rich source of biological regulators.

Author affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

Correspondence to: Matthew Freeman1 Email:

Published online 11 July 2012