NEDD4-L (neural precursor cell expressed, developmentally down-regulated 4-like), also known as RSP5, NEDD4-2 or NEDL3, is a 975 amino acid protein that localizes to the cytoplasm and contains four WW domains, one HECT domain and one C2 domain. Expressed ubiquitously with highest expression in pancreas, prostate and kidney, NEDD4-L functions as an E3 ubiquitin-protein ligase that, characteristic of E3 ligase proteins, accepts ubiquitin (in the form of a thioester) from an E2 ubiquitin-conjugating enzyme and transfers that ubiquitin residue to substrates targeted for degradation. Through its ability to ubiquitinate and induce the proteasome-dependent degradation of proteins such as Smad2 and TGFβ RII, NEDD4-L is thought to inhibit the TGFβ signaling pathway, thereby regulating the signaling pathways that control cell growth and differentiation. NEDD4-L is expressed as eight isoforms due to alternative splicing events.