Homologous to the C‐terminus of E6AP (HECT) and RCC1‐like domain (RLD)‐containing protein 2 (HERC2) is a large, 528 kDa E3 ubiquitin ligase that is associated with cancer, oculocutaneous albanism type 2, Prader‐Willi syndrome, and other neurological diseases. Here, UBE3A is linked to cancer.