Ube2n, a Lys63 ubiquitin-conjugating enzyme, belongs to the UE2s family and plays crucial roles in multiple biological processes. It is involved in DNA repair and is associated with various pathways including the Wnt/β-catenin signaling pathway. Its functions are essential for embryogenesis, immune system development, and maintaining the homeostasis of adult epithelial tissues [3,4,6]. Genetic models, such as knockout mouse models, have been instrumental in studying its functions.

In prostate cancer, Ube2n is upregulated, and its high expression correlates with poor prognosis. Knocking down Ube2n inhibits cell viability and glycolysis in prostate cancer cells and restricts tumor formation in tumor-bearing mice [1]. In Alzheimer's disease, Ube2n levels are elevated during amyloid beta (Aβ) deposition. Overexpression exacerbates amyloid deposition, while knockdown reduces Aβ generation and cognitive deficiency. Pharmacological inhibition also ameliorates Aβ pathology [2]. In the skin, Ube2n knockout in adult skin keratinocytes induces inflammatory skin defects characteristic of psoriatic and actinic keratosis, highlighting its role in maintaining epidermal homeostasis and skin immunity [3,6]. In acute myeloid leukemia, Ube2n is required for leukemic cell function, and its inhibition disrupts oncogenic immune signaling [5]. In lung adenocarcinoma, Ube2n is highly expressed, and its interference inhibits cancer progression [7]. In ovarian cancer, overexpressed Ube2n enhances paclitaxel sensitivity [8].

In conclusion, Ube2n is essential for maintaining normal physiological functions and is closely associated with multiple diseases including cancer and Alzheimer's disease. Gene knockout and conditional knockout mouse models have significantly contributed to understanding its functions in these disease areas, providing potential therapeutic targets for treatment.