<p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra. Although familial and sporadic forms of PD have distinct etiological origins, they converge on overlapping molecular pathways that remain incompletely understood. In this study, we aimed to identify shared "hub genes" that may drive DA neuron degeneration across both PD subtypes. We reanalyzed gene expression profiles from three publicly available datasets comprising DA neuron samples derived from postmortem human midbrains and patient-induced pluripotent stem cell-derived DA neurons. Twelve hub genes were consistently dysregulated across all datasets. Functional annotation revealed that these genes are critically involved in membrane trafficking and vesicle-mediated transport—key processes for maintaining neuronal integrity and synaptic function. Network-based analysis further linked these hub genes to a range of other neurological and systemic disorders, indicating broader relevance to disease biology. Experimental validation in neurotoxin-exposed SH-SY5Y cell models of PD confirmed significant dysregulation of several candidate genes at both mRNA and protein levels. Moreover, RNAi-mediated silencing of a key hub gene in <i>Caenorhabditis elegans</i> led to enhanced DA neuron degeneration, reinforcing its functional role in neuronal survival. Together, these findings identify a set of conserved molecular drivers of DA neuron vulnerability and propose novel therapeutic targets for both familial and sporadic PD.</p> Graphical abstract <p></p>