Proteasomes are large multicatalytic proteinase complexes which fulfill key functions in both ubiquitin-dependent and ubiquitin- independent non-lysosomal pathways of protein breakdown in the cell. 20 S proteasomes are 700 kDa cylindrically shaped particles, found in the cytoplasm and the nucleus of all eukaryotes. They are composed of a pool of 14 different subunits (molecular mass 22-31 kDa) arranged in a stack of 4 rings with 7-fold symmetry. 26 S proteasomes are even larger proteinase complexes (about 2000 kDa) which degrade ubiquitinylated proteins in an ATP-dependent fashion in vitro. The 26 S proteasome is build up from the 20 S proteasome as core particle and two additional 19 S complexes at both ends of the 20 S cylinder. Proteasomes contain at least five distinct types of catalytic components and are capable of degrading proteins to small peptides. They are particularly involved in the degradation of short-lived and regulatory proteins. The proteasome has been highly conserved during eukaryotic evolution, and simpler forms are even found in archaebacteria and eubacteria.