The ubiquitin-proteasome system (UPS) is a multi-step process that serves as the primary pathway for protein degradation within cells. UPS activity also plays a crucial role in regulating various life processes, including the cell cycle, signal transduction, DNA repair, and others. The F-box protein Skp2, a crucial member of the UPS, plays a central role in the development of various diseases. Skp2 controls cancer cell growth and drug resistance by ubiquitinating modifications to a variety of proteins. This review emphasizes the multifaceted role of Skp2 in a wide range of cancers and the mechanisms involved, highlighting the potential of Skp2 as a therapeutic target in cancer. Additionally, we describe the impactful influence exerted by Skp2 in various other diseases beyond cancer.
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