Fbxo2, a member of the F-box proteins (FBPs) family, is a substrate recognition component of the Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex with specificity for high-mannose glycoproteins. It is involved in multiple biological processes such as xenophagy, the regulation of protein degradation via the ubiquitin-proteasome system, and may play a role in inner ear cell manipulation as indicated by the Fbxo2CreERT2 mouse model [5,6].

In cancer, gene knockout studies have revealed its oncogenic role. In osteosarcoma, FBXO2 knockout (KO) cells showed reduced proliferation and tumorigenicity, and knocking out FBXO2 inhibited STAT3 phosphorylation through IL-6R stabilization [3]. In glioblastoma, FBXO2 knockout in human glioma cells conferred a survival benefit in orthotopic xenograft mouse models and reduced invasive growth [2]. In ovarian cancer, FBXO2 targets glycosylated SUN2 for ubiquitination and degradation, promoting cancer development, and manipulation of its expression affected cancer cell behavior [1]. In papillary thyroid carcinoma, silencing FBXO2 inhibited cell proliferation and promoted apoptosis by targeting p53 for ubiquitination and degradation [4]. In gastric cancer, knockdown of FBXO2 decreased cell proliferation and migration and reduced epithelial-mesenchymal transition (EMT) [7]. In endometrial cancer, FBXO2 knockdown inhibited cell proliferation, and it was found to target FBN1 for ubiquitin-dependent degradation to promote cancer cell proliferation [8].

In summary, Fbxo2 is essential in processes related to protein degradation and cell regulation. Gene knockout mouse models have significantly contributed to understanding its role in various cancers, highlighting its potential as a therapeutic target in cancer treatment. Additionally, it may have a role in non-cancerous processes like inner ear cell manipulation and xenophagy [1-9].