Uba2, also known as ubiquitin-like modifier activating enzyme 2, is a subunit of the E1-activating enzyme involved in the SUMOylation (small ubiquitin-related modifier) of numerous proteins. SUMOylation participates in regulating various cellular processes such as DNA-repair by nonhomologous end-joining, and thus is crucial for nearly all physiological and pathological cellular processes [8].

Uba2 has been associated with multiple diseases. In cancers like hepatocellular carcinoma (HCC), glioma, renal cell carcinoma, colorectal cancer, and lung cancer, its overexpression is linked to aggressive behaviors, poor prognosis, and enhanced cell proliferation, invasion, and migration. For example, in HCC, Uba2 SUMOylates NQO1 and promotes proliferation by modulating the MAPK pathway [1]. In glioma, its expression correlates with clinicopathological features and high expression predicts poor survival, and knockdown suppresses cell progression [2]. In renal cell carcinoma, Uba2 promotes tumor progression by suppressing the p53 signaling [4]. In colorectal cancer, downregulation of Uba2 inhibits cell proliferation both in vitro and in vivo [5]. In lung cancer A549 cells, knockdown of Uba2 inhibits cell proliferation and upregulates apoptosis [6]. In addition, Uba2 variants can cause a syndrome with features like aplasia cutis congenita and ectrodactyly, indicating its importance in development [3]. In acute myeloid leukemia, the UBA2-WTIP fusion gene has been identified as an oncogenic fusion gene [7]. Also, in rheumatoid arthritis, increased SAE1/UBA2 promotes glycolysis and pathogenic behavior of fibroblast-like synoviocytes [9].

In conclusion, Uba2 is essential in SUMOylation, which is vital for normal cellular functions. Its dysregulation is implicated in multiple diseases, especially various cancers and a specific congenital syndrome. Research on Uba2, including through loss-of-function experiments in different cell lines and in vivo models as seen in the studies, has enhanced our understanding of its role in disease development, potentially providing new therapeutic targets for these diseases.