To investigate whether heat shock protein 70 binding protein 1 (HspBP1) can promote the aggregation of endogenous mutant huntingtin (mHTT) in astrocytes and determine whether it can mediate pathological damage. Methods: HspBP1 was overexpressed in GFAP-HD transgenic mice, and the expression levels of mHTT and neuropathological related proteins were detected by immunostaining and Western blotting. The motor function level of mice was observed by behavioral experiments. Results: mHTT aggregation in astrocytes and motor dysfunction occurred in GFAP-HD transgenic mice within a short period of time, but no activation of astrocytes or neuronal damage was observed. Conclusion: HspBP1 can mediate pathological damage by promoting the accumulation of endogenous mHTT in astrocytes, but the coexpression of mHTT in neurons and astrocytes may be essential for significant neuronal degeneration.