HERC2 is a massive 527 kDa E3 ubiquitin ligase that has been implicated in ulcerative colitis, cancer, Prader‐Willi syndrome, Angelman syndrome, and other neurological diseases (Bekker‐Jensen et al. 2010; Bonanno et al. 2016; Cubillos‐Rojas et al. 2017; Franke et al. 2008; Harlalka et al. 2013; Ibarrola‐Villava et al. 2010; Imai et al. 2015; Izawa et al. 2011; Ji et al. 1999; Liu et al. 2023; Puffenberger et al. 2012). Here, HERC2 is linked to Angelman syndrome.