In PD, ASC specks significantly amplified the activation of NLRP3 inflammasome and reactive microgliosis, promoting α‐synuclein pathology in a vicious positive-feedback manner; ASC specks also contributed to earlier occurrence of dopaminergic neurodegeneration and dyskinesia; Knockdown of endogenous ASC markedly suppressed microglial inflammasome activation and neuronal α‐synuclein aggregation under the challenge of PFFs. Here, NLRP3 is linked to Parkinson disease.