HSP70

HSP70 (Heat Shock Protein 70) is a highly conserved ATP-dependent molecular chaperone that maintains proteostasis by promoting protein folding, preventing aggregation of misfolded proteins, facilitating protein complex remodeling, and supporting protein translocation across cellular membranes^[1][2]. Mechanistically, HSP70 functions through an ATP-regulated chaperone cycle in which substrate recognition, ATP hydrolysis, and co-chaperone interactions determine whether client proteins are refolded or directed toward degradation pathways^[1]. This central role links HSP70 to cellular stress adaptation, because its expression increases in response to environmental and physiological stressors and helps preserve protein homeostasis under conditions that promote protein damage^[3][4]. In disease models, impaired proteostasis and reduced chaperone capacity are associated with the accumulation of toxic misfolded proteins, whereas enhanced HSP70 activity has been linked to reduced protein aggregation, inflammation, and neuronal loss in neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis^[5]. Compared with related heat shock protein families such as HSP90, HSP70 is distinguished by its direct engagement with unfolded polypeptides and its prominent role in determining protein refolding versus degradation outcomes through co-chaperone-dependent quality-control mechanisms^[1]. For experimental applications, HSP70 has become an important therapeutic research target, and both pharmacological modulators and recombinant HSP70-based approaches are widely investigated to manipulate proteostasis, cytoprotection, and stress-response pathways in models of neurodegenerative, inflammatory, and other protein-misfolding-associated diseases^[1][6].