By uncovering the DNMT3A-STAT5B-MBP axis in PD pathogenesis, we reveal how oligodendrocyte epigenetic dysregulation drives dopaminergic circuit failure, propose STAT5B reactivation as a dual-target therapy for myelin repair and neuroprotection, and nominate STAT5B promoter methylation as a translatable progression biomarker. Here, DNMT3A is linked to Parkinson disease.