E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates such as LCMT2, thereby promoting their degradation. Induces apoptosis via a p53/TP53-dependent but caspase-independent mechanism. Plays a crucial role in maintaining the genomic stability by controlling the degradation of multiple proteins involved in mitotic progression and DNA damage (PubMed:38685100). Regulates epithelial homeostasis by mediating degradation of CDKN1A and isoform 2 of TP63 (PubMed:23128396). Plays a regulatory role in innate immunity by negatively regulating IRF3 activation and IFN-beta production. Mechanistically, inhibits TBK1 phosphorylation and 'Lys-63'-linked polyubiquitination independently of its E3 ligase activity (PubMed:31509299). Alternatively, promotes 'Lys-27' and 'Lys-33'-linked ubiquitination of IFIH1/MDA5, promoting selective autophagic degradation of IFIH1/MDA5 to inhibit antiviral response (PubMed:39285245). {ECO:0000269|PubMed:12853982, ECO:0000269|PubMed:20300062, ECO:0000269|PubMed:23128396, ECO:0000269|PubMed:31509299, ECO:0000269|PubMed:39285245}. This is the function of ENSG00000137393 (RNF144B, ring finger protein 144B).