Abstract
Chaperonins, evolutionarily conserved heat shock proteins characterized by subunits of approximately 60 kDa, play indispensable roles in maintaining cellular homeostasis. In eukaryotes, chaperonins include primarily HSP60 and TRiC, with HSP60 being a crucial mitochondrial chaperonin and TRiC being an essential cytosolic chaperonin. The two fundamental functions of chaperonins are assisting proteins in acquiring and maintaining their activity under physiological conditions and initiating stress responses under stressful conditions. Chaperonins also indirectly regulate biological processes such as mitochondrial function, cytoskeleton organization, the cell cycle, immunity, autophagy, and apoptosis. Owing to the biological fundamentality and cross-species conservation of chaperonin functions, diseases associated with chaperonins-such as genetic disorders, neurodegenerative disorders, cardiovascular diseases, inflammatory diseases, autoimmune diseases, infectious diseases, and neoplastic diseases-can affect most eukaryotes throughout their entire lifespan and involve multiple systems and organs. Consequently, chaperonins have emerged as valuable non-invasive biomarkers for disease diagnosis and prognosis, as well as highly promising therapeutic targets for intervention. This article provides a detailed review of the current research status and progress regarding the pathogenic mechanisms of chaperonins in human diseases, related drug development, and clinical applications. It aims to offer basic researchers, drug developers, and clinicians a perspective on diseases through the lens of chaperonins, thereby promoting the translation of related research findings into clinical applications.