Particularly, upon DCD liver IR insult, the DOC and HECT domains of HECTD3 directly bind to TRAF3, and the C832 of the HECT domain promotes the K63-linked polyubiquitination of TRAF3 at Lys138 to trigger oxidative stress and inflammatory response, thereby leading to serious liver IRI. Here, HECTD3 is linked to digestive system neoplasm.