Fbxo45, an F-box protein, is a substrate-recognition subunit of E3 ligases. It is involved in many biological processes and diseases. E3 ligases play a crucial role in the ubiquitination pathway, which tags proteins for degradation, thus regulating various cellular functions. Fbxo45 is associated with multiple diseases including nervous system diseases, inflammatory diseases, and human malignancies [1].

In cancer, Fbxo45 has been shown to have oncogenic functions. In pancreatic cancer, Fbxo45 promotes carcinoma progression by targeting USP49 for ubiquitination and degradation, enhancing cell viability and motility [2]. In breast cancer, down-regulation of Fbxo45 inhibits cell proliferation and induces apoptosis, while its overexpression has the opposite effects, and it targets Bim for ubiquitination and degradation [3]. In liver cancer, highly expressed Fbxo45 promotes liver tumorigenesis through enhancing IGF2BP1 ubiquitination and subsequent PLK1 upregulation [4]. In lung cancer, Fbxo45-mediated NP-STEP46 degradation via K6-linked ubiquitination sustains ERK activity and promotes tumor growth, and its silencing can increase sensitivity to EGFR-TKI therapy [6]. In esophageal squamous cell carcinoma, Fbxo45 promotes the malignant development by targeting GGNBP2 for ubiquitination and degradation [7].

In conclusion, Fbxo45 is a key player in cancer development through its role in regulating the stability of various proteins via ubiquitination. The findings from these studies using in-vitro and in-vivo models, especially in cancer-related research, provide valuable insights into the potential of targeting Fbxo45 for cancer treatment. Additionally, Fbxo45 may also have functions in neuron migration during brain development [8] and in restricting HIV-1 replication [5].