New neuroimaging studies have charted progressive loss of nigral volume across prodromal, early, and moderate stages of Parkinson’s disease (PD), utilizing advanced MRI techniques sensitive to iron and neuromelanin. Complementary cellular research revealed mutation-specific lysosomal and mitochondrial dysfunctions in dopamine and cortical neurons, extending understanding of PD heterogeneity. These findings offer refined biomarkers and stress the necessity for mutation-tailored therapeutic strategies.