[5] Members of the Hsp70 family are very strongly upregulated by heat stress and toxic chemicals, particularly heavy metals such as arsenic, cadmium, copper, mercury, etc.

Heat shock was originally discovered by Ferruccio Ritossa in the 1960s when a lab worker accidentally boosted the incubation temperature of Drosophila (fruit flies).

When examining the chromosomes, Ritossa found a "puffing pattern" that indicated the elevated gene transcription of an unknown protein.

A 2020 publication suggests that phosphorylation of a serine residue between the NBD and substrate binding domain in yeast Hsp70s leads to a dramatic reduction of the normal Hsp70 heat shock response.

As newly synthesized proteins emerge from the ribosomes, the substrate binding domain of Hsp70 recognizes sequences of hydrophobic amino acid residues, and interacts with them.

This spontaneous interaction is reversible, and in the ATP bound state Hsp70 may relatively freely bind and release peptides.

However, the presence of a peptide in the binding domain stimulates the ATPase activity of Hsp70, increasing its normally slow rate of ATP hydrolysis.

By binding tightly to partially synthesized peptide sequences (incomplete proteins), Hsp70 prevents them from aggregating and being rendered nonfunctional.

By temporarily binding to hydrophobic residues exposed by stress, Hsp70 prevents these partially denatured proteins from aggregating, and inhibits them from refolding.

Although the maximum lifespan increased only moderately, the overall mortality rate in treated animals was much lower compared with the control group.

[43] HSP70 helps in protecting skin against the increased melanin and wrinkled formation induced due to UV exposure.

Diabetes leads to several microvasculature and microvasculature diseases like retinopathy, Toll like receptors are integral part of innate immune system and eHSP70 binds to toll like receptors and activates the MyD88 pathway, further stimulating NF-kB, cytokines like TNFα and IL1 β, increased production of reactive oxygen species contributing to insulin resistance and diabetes.

HSP70 normally aids in protein folding and aggregation; when present in the cell, functioning as an anti-inflammatory molecule; however, under stress conditions, it is localized to the extracellular milieu, where it is involved in inducing inflammatory pathways and contributes to disease pathogenesis.

This activates HSP70 and its promoter in the endothelial and smooth muscle cells, which contributes to atherosclerosis by inducing JAK/STAT pathway expression.

[58][59] HSP70 is also linked to high blood pressure, a worldwide concern and risk factor for a variety of cardiovascular diseases.

Hypertension causes endothelial dysfunction and vascular wall damage, both of which contribute to arterial stiffness and atherosclerosis.

[60] HSPA1A, HSPA1B, and HSPA1L are three genes in humans that encode HSP70, and their polymorphism is linked to the onset of high blood pressure and cardiovascular disease.

Exercise has a positive and protective impact on cardiovascular disorders and stimulates the increased production of chaperone protein together known to be cardioprotective.

These are, among others: The following is a list of human Hsp70 genes and their corresponding proteins:[2] HSP70s are found in many plants including Arabidopsis, soybean (Glycine max), barley (Hordeum vulgare) and wheat (Triticum aestivum).

DnaK initially binds and stabilizes the misfolded protein before working collaboratively with Hsp90Ec to refold this substrate and cause its activation.