This dataset presents a high-resolution, label-free quantitative (LFQ) bottom-up proteomic analysis profiling the molecular rearrangements within the cerebellar tissue architecture following the knockdown of the wingless-type MMTV integration site family, member 10B (Wnt10b) ligand. Using organotypic slice cultures derived from the postnatal mouse cerebellum, this study captures systemic disruptions in cellular homeostasis, with a strong functional enrichment of differentially expressed proteins mapping directly to localized translational machinery at both pre-synaptic and post-synaptic densities. The dataset serves to bridge transcriptional disruptions in the YY1-Wnt10b signaling axis with precise downstream synaptic proteostasis failures driving ataxic phenotypes.