Abstract In recent years, the biological functions of rubidium ions (Rb+) and their associations with neurological disorders have garnered increasing attention. Accumulating evidence suggests that dysregulation of Rb+ metabolism may be involved in the onset and progression of Parkinson’s disease (PD), although the precise molecular mechanisms remain unclear. This study systematically integrates existing experimental data and theoretical models to investigate the potential roles of Rb+ in neuronal electrical activity, mitochondrial function, and α-synuclein aggregation, and evaluates its feasibility as a disease biomarker or therapeutic target. Our analysis indicates that Rb+ can alter neuronal excitability by interfering with Na+/K+-ATPase activity; elevated Rb+ levels may further exacerbate mitochondrial membrane potential reduction, increase reactive oxygen species (ROS) accumulation, and promote α-synuclein fibrillization. In PD animal models, changes in Rb+ levels correlate positively with microglial activation and dopaminergic neuronal loss. Based on these observations, we propose a theoretical framework in which dysregulated Rb+ metabolism contributes to PD pathology through multiple mechanisms, potentially promoting neurodegeneration. This hypothesis provides a novel perspective for understanding PD pathogenesis and suggests that modulation of Rb+ homeostasis could represent a potential intervention strategy. Graphical abstract Highlights Na+/K+ homeostasis links Rb+ to Parkinson’s disease pathology Rb+ imbalance intersects with core pathogenic pathways in PD TCM formulas may indirectly regulate Rb+ homeostatic networks In Brief This review proposes a theoretical framework linking rubidium (Rb+) metabolic dysregulation to Parkinson’s disease through mitochondrial dysfunction, oxidative stress, neuroinflammation, α-synuclein aggregation, and ionic imbalance. It further explores how Traditional Chinese Medicine–mediated signaling and ion transport modulation may indirectly influence Rb+ homeostasis and disease progression.
Lichun Zhao (Wed,) studied this question.