HECTD3 is a E3 ubiquitin ligase of the HECT family that plays critical roles in several inflammatory disease, including inflammation-related tumor metastasis [19], bacterial infection [20], RNA virus infection [21] and experimental autoimmune encephalomyelitis [22] etc., but its contribution to NLRP3 inflammasome remains unknown. Here, HECTD3 is linked to experimental autoimmune encephalomyelitis.