Fbxo9, an F-box protein, serves as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase. It is involved in multiple cellular processes such as cell proliferation, apoptosis, migration, and is associated with pathways like V-ATPase assembly, Wnt signaling, and the ubiquitin-proteasome system [1,2,4]. It has significance in various biological contexts including cancer, cell fate determination, and adipocyte differentiation, making genetic models crucial for its study.

In cancer, loss-of-function experiments have shown diverse effects. In lung cancer, knockdown of Fbxo9 increased V-ATPase assembly, vesicular acidification, pro-metastatic Wnt signaling, and metastasis, indicating its tumor-suppressive role [1]. In hepatocellular carcinoma, FBXO9 facilitated cell proliferation and metastasis, and its knockdown increased sensitivity to drugs [2]. In acute myeloid leukemia, deletion of Fbxo9 in a murine hematopoietic system using a CRISPR/Cas9-based conditional knockout mouse model led to accelerated and aggressive leukemia development, and tumors lacking Fbxo9 had increased proteasome activity [3]. In osteoclasts, knockdown of FBXO9 induced ferroptosis [5].

In conclusion, Fbxo9 plays essential roles in regulating multiple biological processes. Through gene knockout and conditional knockout mouse models, its role in diseases like cancer and cell-specific functions has been revealed. These studies on Fbxo9 enhance our understanding of biological mechanisms and may provide potential therapeutic targets for related diseases.