sHsps have some structural features in common: Very characteristic is a homologous and highly conserved amino acid sequence, the so-called α-crystallin domain near the C-terminus.

These domains consist of 80 to 100 residues with sequence homology between 20% and 60% and fold into β-sheets, which are important for the formation of stable dimers.

The C-terminal region of sHsps consists of the above mentioned α-crystallin domain, followed by a variable sequence with high motility and flexibility.

[14] In the case of Hsp27, the IxI/V motif corresponds to 181-Ile-Pro-Val-183, and this region of the protein plays a critical role, as the mutation of the central Pro residue causes the hereditary motor neuropathy Charcot-Marie-Tooth disease.

[17][18] Hsp27-oligomers consist of stable dimers, which are formed by two α-crystallin-domains of neighboring monomers,[16][11] which was first shown in crystal structures of the proteins MjHSP16.5 from Methanocaldococcus jannaschii[7] and wheat Hsp16.9.

The amino acid sequences in this region, however, are predicted to be disordered [19] Indeed, the α-crystallin domain of Hsp27 partially unfolds in its monomeric state and is less stable than the dimer.

[26] High expression levels possibly are in inverse relation with cell proliferation, metastasis, and resistance to chemotherapy.

[27] High levels of Hsp27 were also found in sera of breast cancer patients;[28] therefore Hsp27 could be a potential diagnostic marker.

The main function of Hsp27 is to provide thermotolerance in vivo, cytoprotection, and support of cell survival under stress conditions.

Hsp27 enhances the activation of the NF-κB pathway, that controls a lot of processes, such as cell growth and inflammatory and stress responses.

[31] The cytoprotective properties of Hsp27 result from its ability to modulate reactive oxygen species and to raise glutathione levels.

[37] Protein kinase C-mediated HSPB1 phosphorylation protects against ferroptosis, an iron-dependent form of non-apoptotic cell death, by reducing iron-mediated production of lipid reactive oxygen species.