Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Proteolysis is usually catalyzed by enzymes known as proteases, but can also occur through intramolecular digestion. Low pH or high temperature can also cause proteolysis without enzymolysis. In eukaryotes, there are two main mechanisms of protein degradation, lysosome and 26S proteasome. Lysosomes mainly deal with long-lived proteins in a non-selective manner, while proteasomes degrade abnormal or short-lived proteins in a strictly regulated manner. Proteasome and lysosome are the two major proteolytic sites in eukaryotic cells. They degrade various proteins, but most of their substrates have very different properties, and there is not much overlap between the two systems. It is noteworthy that many studies have suggested the role of proteasomes in many pathological diseases, such as cancer and Alzheimer's disease.