SKP2 (S-phase kinase associated protein 2) functions as a substrate adaptor protein in the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, mediating the ubiquitin-dependent proteasomal degradation of key regulatory proteins 1. The protein plays critical roles in cell cycle progression by targeting cyclin-dependent kinase inhibitors p27 and p57 for degradation, promoting S-phase entry and preventing cellular differentiation 23. SKP2 catalyzes both K48-linked ubiquitination for proteasomal degradation and K63-linked ubiquitination for protein stabilization, as demonstrated with PD-L1 in cancer cells 4. In disease contexts, SKP2 overexpression contributes to tumorigenesis across multiple cancer types by dysregulating cell cycle control and differentiation pathways 52. The protein's subcellular localization is regulated by acetylation, with cytosolic accumulation leading to p27 hyper-accumulation and polyploidy 3. SKP2 expression correlates with tumor stage, grade, and poor prognosis in various cancers, making it an attractive therapeutic target 56. Additionally, SKP2 participates in pulmonary fibrosis progression through p27 degradation-mediated fibroblast proliferation 7.