This E3 ligase induces tumorigenesis by modulating post-translational stability or functions of various substrates with the tumor suppressive activity, such as PTEN (Lee et al. 2019; Lee et al. 2020b), TGF-β type 1 receptor (Komuro et al. 2004), SMADs (Morén et al. 2005; Seo et al. 2004), p63 (Li et al. 2008; Chen et al. 2018), p53 (Laine and Ze 2007), p27kip (Sanarico et al. 2018; Cao et al. 2011), and HER4/ErbB4 (Feng et al. 2009; Li et al. 2009) as well as those with the tumor-promoting activity such as CK2β (Kim et al. 2018) and DVL2 (Nielsen et al. 2019; Zhao et al. 2021). Here, ERBB4 is linked to neoplasm.