The N-end rule pathway is a ubiquitin-dependent proteolytic system, in which 
destabilizing N-terminal residues of short-lived proteins function as an 
essential determinant of an N-terminal degradation signal (N-degron). An 
N-degron can be created from a pre-N-degron through specific N-terminal 
modifications, providing a means conditionally to destabilize otherwise stable 
polypeptides. The pathway has been found in all organisms examined, from 
prokaryotes to eukaryotes. Recent biochemical and proteomic studies identified 
many components of the mammalian N-end rule pathway, including a family of 
substrate recognition ubiquitin ligases and their substrates. The genetic 
dissection in animals and humans revealed its essential role in various vital 
physiological processes, ranging from cardiovascular development and meiosis to 
the pathogenesis of human genetic diseases. These discoveries have provided new 
insights into the components, functions and mechanics of this unique proteolytic 
system.