Abstract
FBXW5, a member of the F-box protein family, plays a pivotal role in various cellular processes through its involvement in ubiquitin-mediated proteolysis as a component of the SCF complex. Recent studies have highlighted the potential of targeting FBXW5 for therapeutic interventions, making it a promising candidate for drug development. Thus, it is of great importance to provide a comprehensive overview of the structure and function of FBXW5, with a particular focus on its binding motifs for gene regulation and activities to recruitment and recognition. Herein, this review summarizes the biological significance of FBXW5 in different diseases, including cancers, neurological disorders, and other pathological conditions. This review also discusses the current challenges and future perspectives in research on FBXW5 in human diseases. Although direct inhibitors are lacking, therapeutic vulnerability is achieved via SCF inhibition or targeting hyperactivated downstream signaling nodes, emphasizing the need for further studies to fully elucidate its biological functions and therapeutic potential.