E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with TSG101 (PubMed:17556548). Interacts with PHF23 (PubMed:25484098). Interacts with FUS (PubMed:27615052). Displays a punctuate distribution and localizes to a submembranal ring (PubMed:15256501). Localizes to intracellular bacterial pathogens (PubMed:23245322). Highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue. The coiled coil domains interact with the SB domain of TSG101. The PTAP motifs mediate the binding to UEV domains. The LRR domain is necessary and sufficient for localization to bacterial targets. The RING domain is required for ubiquitination. Ubiquitination promoted by PHF23 leads to proteasomal degradation. The disease is caused by variants affecting the gene represented in this entry.