RPS27A encodes ribosomal protein S27a, a component of the 40S ribosomal subunit that plays essential roles in protein synthesis and cellular regulation 1. RPS27A is initially expressed as a ubiquitin-RPS27A fusion protein (Uba80), from which ubiquitin is cleaved by deubiquitinating enzymes, allowing both proteins to function independently 12. Beyond its structural role in ribosomes, RPS27A functions as a regulatory protein in multiple cellular processes. It serves as a protein scaffold that facilitates interactions between ribosomal proteins, such as promoting RPS27A-RPL11 binding, which influences c-Myc activity and downstream signaling pathways 3. RPS27A is subject to site-specific ubiquitination by E3 ligase RNF25 during ribosome quality control, contributing to the degradation of stalled translation factors 4. The protein also stabilizes other oncoproteins through deubiquitination mechanisms, as demonstrated by its interaction with USP9X to stabilize PPP1R14B in triple-negative breast cancer 5. Clinically, RPS27A dysregulation is associated with various cancers including hepatocellular carcinoma, prostate cancer, and contributes to poor prognosis and chemotherapy resistance 163. Additionally, RPS27A has been identified as a potential biomarker in neurodegenerative diseases, with network analysis suggesting it may serve as a key upstream regulator in Alzheimer's disease pathogenesis 7.