New studies illuminate molecular mechanisms central to Parkinson’s disease (PD). Investigations reveal that parkin-deficient human dopaminergic neurons derived from iPSCs generate α-synuclein aggregates with enhanced seeding activity, advancing understanding of pathological protein propagation. Furthermore, mutations linked to PD cause neuron-specific mitochondrial and lysosomal dysfunction, underscoring mutation-dependent pathology. The Michael J. Fox Foundation’s Targets to Therapies initiative is accelerating validation of 21 prioritized targets through focused collaborative efforts. Meanwhile, butyrate supplementation improved sleep disturbances in PD mouse models via BDNF-TrkB pathway modulation, suggesting new non-motor symptom interventions.