The problem of different sensitivities of distinct protein groups to lysosomal inhibitors has remained unsolved and may have served as an important trigger in the future quest for a non-lysosomal proteolytic system that may be involved in at least certain aspects of intracellular protein degradation.

The development of methods to monitor protein dynamics in cells together with the discovery of specific and general lysosomal inhibitors have resulted in the identification of different classes of cellular proteins, long- and short-lived, and the findings of the differential effects of the inhibitors on these groups.

Reticulocytes are terminally differentiating red blood cells that do not contain lysosome. Therefore, it was postulated that the degradation of hemoglobin in these cells is mediated by a non-lysosomal machinery.

Aaron Ciechanover Quotes