NEDD4L has been identified as an E3 ligase that mediates the ubiquitination and downregulation of PIK3CA, the catalytic subunit of class IA PI3Ks, thereby inhibiting the PI3K-AKT signaling pathway and VEGFA secretion in breast cancer (Kok et al., 2009; Wang et al., 2016; Guo X. Y. et al., 2022). The gene discussed is PIK3CA; the disease is breast cancer.