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Current pharmacological therapies remain limited to symptomatic management, owning to an incomplete understanding of the mechanisms driving \u03b1\u2011synuclein aggregation and disease progression. This review provides an integrated overview of PD across epidemiological, etiological, pathophysiological, and clinical dimensions. It emphasizes established and emerging risk factors, including environmental toxins, lifestyle variables, and gut microbiota dysbiosis and delineates how peripheral\u2013central pathways such as the gut\u2013brain, erythrocyte\u2013brain, and kidney\u2013brain axes contribute to PD pathogenesis. At the molecular level, we explore key disruptions including proteostatic failure, aberrant phase separation, oxidative stress, neuroinflammation, synaptic dysfunction, iron dyshomeostasis, and impaired cholesterol metabolism. These encompass microbiome\u2011targeted interventions and blood\u2010based approaches. We further evaluate a spectrum of management strategies ranging from primary prevention and biomarker\u2011guided early detection to innovative experimental treatments such as cellular therapies, transfusion\u2011based modalities, and microbial modulation. By integrating recent advances in systemic pathophysiology with translational perspectives, this review highlights how molecular and cellular dysregulations underlie clinical phenotypes. 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