 The hektite E3 ubiquitin ligase family plays a crucial role in regulating autophagy, a process by which cells break down and recycle proteins and organelles. This process is important for maintaining cellular homeostasis and preventing diseases such as cancer. Recent studies have shown that certain members of this family, including NEDD4-1, NEDD4-L, SMURFs, WWPS, and ITCH, are involved in defective autophagy in cancer cells. These E3 ligases can target specific substrates and interact with other proteins to regulate autophagy, providing a potential therapeutic target for treating cancer. This article was authored by Rui Zhong and Xiao Qingxia.