Uhrf2, also known as Ubiquitin-like with PHD and ring finger domains 2, is a protein-coding gene. It functions as an E3 ubiquitin ligase, catalyzing the ubiquitination of target proteins. It is involved in multiple biological processes such as regulating gene expression, DNA demethylation, cell cycle, and is associated with pathways like Wnt/β-catenin, ErbB3/Ras/Raf, and DNA damage response pathways [1,2,4,6,7]. Genetic models, especially knockout (KO) mouse models, have been crucial in understanding its functions.

In Uhrf2 -/- mice, the repopulating ability of hematopoietic progenitor cells was impaired, suggesting its role in hematopoiesis [3]. In intestinal tumorigenesis, Uhrf2 null mice on an ApcMin background showed inhibited tumor initiation and progression, indicating Uhrf2 promotes intestinal tumorigenesis through stabilizing TCF4-mediated Wnt/β-catenin signaling [4]. In retinal development, conditional deletion of Uhrf2 from mouse retinal progenitor cells (RPCs) disrupted retinal cell proliferation and differentiation [5]. Hepatocyte-specific Uhrf2 knockout in mice caused extensive liver necrosis and impaired hepatocyte proliferation after partial hepatectomy, highlighting its essential function in liver regeneration [8].

In conclusion, Uhrf2 is essential for various biological processes. The study of Uhrf2 KO and conditional knockout (CKO) mouse models has revealed its role in diseases like hepatocellular carcinoma, intestinal tumors, and has implications in hematopoiesis, retinal development, and liver regeneration. These models have significantly contributed to understanding Uhrf2's function, providing potential targets for therapeutic intervention in related diseases.