M4 confirms mGluR1-PLC-IP3R1 signaling pathway dysregulation as a central mechanism of SPN dysfunction in HD, with our temporal analysis revealing progressive collapse across SPN subtypes and predicting roles of network hub genes involved both epigenetic (Zswim6) and post-transcriptional (Rbfox1, Celf2) regulation. Here, CELF2 is linked to Huntington disease.