Ubb, the polyubiquitin gene, encodes ubiquitin, a highly conserved eukaryotic protein pivotal in cellular signal transduction, differentiation, and proteolysis. Ubiquitin, via the ubiquitin-proteasome system (UPS), is crucial for removing damaged and redundant proteins, thus maintaining cellular proteostasis [2].

Disruption of the Ubb gene in KO mouse models leads to various pathological outcomes. In mice, Ubb disruption causes retinal degeneration, as seen by a decreased thickness of the outer nuclear layer of the retina, reduced rhodopsin levels, and increased glial fibrillary acidic protein levels, indicating that Ub pools in the retina are vital for photoreceptor cell survival [3]. Additionally, Ubb KO NSCs show decreased self-renewal capacity, with reduced proliferation markers and thinner ventricular zones in embryonic brains, suggesting cell-autonomous defects due to Ubb disruption contribute to dysregulated neuron differentiation [4]. In clear cell renal cell carcinoma (ccRCC), UBB is downregulated, which is associated with adverse patient survival. It regulates VEGFA by interacting with SP1, influencing angiogenesis, and an unbalanced UBB/VEGFA ratio mediates pazopanib resistance [1].

In conclusion, Ubb is essential for maintaining normal cellular functions, especially in neural-related tissues. Studies using KO mouse models have revealed its role in retinal health, neural stem cell self-renewal, and in the context of ccRCC angiogenesis and drug resistance. These findings enhance our understanding of related biological processes and disease mechanisms, potentially guiding future therapeutic strategies.