IRAK4, a central kinase in TLR/IL-1 signaling36, was identified as a key upstream regulator and directly connected to PPP2R1A, a serine/threonine phosphatase implicated in neurodegeneration37, as well as RIPK1, a kinase involved in cell death and inflammation that is elevated in the brains of PD mouse models38. Here, IRAK4 is linked to Parkinson disease.