E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation. Mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation. Controls ligand-induced EGFR signaling via mediating receptor ubiquitination and recruitment of the ESCRT machinery. Acts as a negative feedback mechanism controlling TLR3 trafficking by mediating TLR3 'Lys-63'-linked polyubiquitination to reduce type I IFN production. Modulates inflammation by promoting caveolin-1/CAV1 ubiquitination and degradation to regulate TLR4-activated immune response.