While previous studies have implicated general WNT signaling abnormalities in neurodegenerative disease,42,43 our work specifically delineates the noncanonical WNT5B‒NFATc2 pathway as a bona fide mechanism underlying HD pathology and identifies it as a potential therapeutic target for HD and related neurodegenerative diseases.43 Both the knockdown of WNT ligands and the downstream transcription factor pangolin/TCF ameliorate survival in the Drosophila HD model.44 In this study, we discovered that WNT5B is upregulated in the striatal astrocytes of HD patients and HD model mice. This evidence concerns the gene HNF4A and Huntington disease.