RNF144B is an E3 ubiquitin ligase with diverse regulatory functions across multiple cellular processes. As a primary function, RNF144B mediates protein degradation by accepting ubiquitin from E2 enzymes and transferring it to target substrates, promoting their ubiquitination and subsequent degradation 1. The protein functions through distinct mechanisms depending on the cellular context. In cancer biology, RNF144B acts as a tumor suppressor by controlling degradation of proteins involved in mitotic progression and DNA damage response, thereby maintaining genomic stability 1. However, it can also exhibit oncogenic properties in certain cancer types 2. In innate immunity, RNF144B negatively regulates antiviral responses through two mechanisms: inhibiting TBK1 phosphorylation and polyubiquitination independently of its E3 ligase activity 3, and promoting K27/K33-linked ubiquitination of MDA5 for autophagic degradation 4. RNF144B also regulates spermatogonial stem cell proliferation and apoptosis via the FCER2/NOTCH2/HES1 pathway 5. Clinically, RNF144B deficiency is associated with genomic instability and worse prognosis in lung adenocarcinoma 1, while mutations are linked to male infertility and azoospermia 5. The protein shows species-specific expression patterns, being LPS-inducible in human but not mouse macrophages 6.