In addition, OTUD4 is down-regulated in radiotherapy-resistant nasopharyngeal carcinoma (NPC), leading to radiotherapy resistance and poor clinical outcomes; OTUD4 was identified as a deubiquitinating enzyme of gasdermin-E (GSDME) proteins, and overexpression of OTUD4 enhances radiosensitization of NPC cells by initiating a GSDME-dependent pyroptosis pathway [68] (Fig. 4). Here, OTUD4 is linked to nasopharyngeal carcinoma.