In most cells, cotransfection with HSPB8 blocked inclusion formation. Biochemical analyses indicated that HSPB8 inhibited the accumulation of insoluble Htt43Q as efficiently as HSP40 (DNAJB1), which was taken as a positive control. Htt43Q then accumulated in the SDS-soluble fraction, provided that protein degradation was blocked by proteasome and autophagy inhibitors. In contrast, HSPB1 and alpha-B-crystallin (CRYAB) had no effect. Analyses of HSPB1/HSPB8 chimeric proteins indicated that the C-terminal domain of HSPB8 contains the specific sequence necessary for chaperone activity.

The K141N mutation significantly reduced the chaperone activity of the protein. Carra et al. (2005) hypothesized that a decrease in HSPB8 chaperone activity may contribute to the development of some neuropathies.