Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.

由于异常折叠蛋白的产生增加或清除减少而导致的蛋白毒性应激（IPTS）增加被认为是一大类高度致残和危及生命的人类疾病（例如神经退行性疾病和许多心脏病）的重要致病因素。蛋白酶体对于及时清除异常蛋白质至关重要，但其功能在疾病条件下往往会变得不足；因此，蛋白酶体功能不足会加剧 IPTS。蛋白酶体生物学的最新研究表明，蛋白酶体可以被内源性蛋白激酶激活，从而可以在药理学上启动蛋白酶体以治疗 IPTS 疾病。