Ube2i, also known as ubiquitin-conjugating enzyme E2I or UBC9, is the sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme. SUMOylation, a post-translational modification process it is involved in, regulates various cellular functions such as protein subcellular localization, transcription, and the cell cycle [1,2,3]. It is important in multiple biological processes and is associated with various diseases.

In adipocytes, deletion of Ube2i in mice (Ube2ia-KO) using CRISPR/Cas9 gene editing and subsequent genetic crosses led to lipoatrophy. These mice developed hyperinsulinemia, hepatic steatosis, and global energy balance defects due to dysfunctional white adipose tissue (WAT) with inflammation, loss of adipokines, and hepatomegaly. This shows that Ube2i in mature adipocytes is crucial for WAT expansion during postnatal growth [1]. In cholangiocarcinoma, knockdown of Ube2i inhibited cell proliferation, delayed xenograft tumor growth, and sensitized cells to chemotherapeutics, likely due to p27kip1 nuclear accumulation and cell cycle arrest [3]. In ovarian cancer, depletion of Ube2i regulated tumor-associated macrophage polarization into M1 type through reprogramming glycolysis and increased the efficacy of anti-PD-L1 immunotherapy [4].

In conclusion, Ube2i is essential for various biological functions. Studies using Ube2i KO mouse models have revealed its significance in adipocyte function and energy balance, as well as in cancer-related processes such as tumorigenesis and immunotherapy response. These findings provide insights into potential therapeutic targets for diseases like lipoatrophy-related metabolic disorders and certain cancers.