This study investigated whether the transcription factor SIX2 mitigates neuroinflammation and provides neuroprotection by promoting microglial M2 polarization and exosome-mediated communication.<h4>Methods</h4>Using LPS-stimulated BV2 microglia and MPTP-induced mouse models of PD, we systematically investigated the role of SIX2. Here, SIX2 is linked to Parkinson disease.