Increasing evidence indicated that E3s, such as CUL3, Nedd4‐2, Synoviolin, FBXL19, PDLIM2, TRIMs and TRAFs, modulate inflammatory responses and bone resorption in periodontitis through multiple classical signalling pathways, including NLRP3, GSDMD, NF‐κB, Wnt/β‐catenin and Nrf2. The gene discussed is NEDD4L; the disease is periodontitis.