NEDD4 is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. NEDD4 plays a significant role in maintaining Golgi structure and function, essential for proper protein sorting and trafficking within cells. NEDD4 interacts with WW domains of several HECT-type E3 ubiquitin ligases, suggesting involvement in ubiquitination processes that regulate protein degradation and cellular signaling pathways. NEDD4 shows high expression in neurons surrounding injury sites, indicating potential neuroprotective functions through ubiquitination modulation, which may contribute to neuronal survival strategies. NEDD4 expression and interaction with E3 ubiquitin ligase Itch increases upon T cell activation, highlighting relevance in immune responses.