RNF20, the human homolog of yeast ubiquitin ligase Bre1, is an E3 ubiquitin ligase crucial for histone H2B monoubiquitination (H2Bub) [1,3,5,6]. It participates in multiple biological pathways, including homologous recombination, epigenetic regulation, and transcriptional control, thus playing an important role in maintaining genome stability, cell differentiation, and organismal development [1,2,3,4,5,6]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in understanding its functions.

In KO mouse models, adipocyte-specific Rnf20 knockout led to progressive fat loss, organomegaly, hyperinsulinemia, and impaired adipose tissue development and thermogenesis, suggesting RNF20's role in adipogenesis, at least in part, through regulating peroxisome proliferator-activated receptor gamma (Pparγ) [8]. RNF20 deletion in mice caused increased inflammation reactions in a sepsis model, indicating its role in suppressing inflammation via the NLRP3 inflammasome and NLRP3 ubiquitination by activating Vitamin D Receptor (VDR) [7].

In conclusion, RNF20 is essential for multiple biological functions, including homologous recombination, epigenetic regulation, and transcriptional control. Its deletion in KO/CKO mouse models reveals its significance in diseases like sepsis and adipose-related disorders, providing insights into the underlying disease mechanisms and potential therapeutic targets.