RPS20 encodes ribosomal protein S20, a structural component of the cytosolic small ribosomal subunit (40S) essential for protein synthesis 1. Beyond its canonical ribosomal function, RPS20 plays critical regulatory roles in cell proliferation and cancer biology. The protein interacts with nucleolar GTPase GNL1 to promote cell cycle progression through retinoblastoma protein hyperphosphorylation, and this interaction is essential for cell growth 2. RPS20 deficiency causes ribosomal shortage and reorganizes cellular translation patterns based on mRNA abundance, GC content, and coding sequence length 3. In disease contexts, RPS20 expression is upregulated in Alzheimer's disease brain capillaries alongside protein processing machinery 4 and functions as an oncogene in renal cell carcinoma by activating AKT-mTOR and ERK-MAPK signaling pathways 5. Paradoxically, germline RPS20 variants predispose to hereditary colorectal cancer, with only rare pathogenic variants reported 6. The protein can undergo post-translational sulfhydration, which enhances its binding to MCM2 mRNA and promotes intestinal epithelial proliferation, potentially protecting against colitis 7. These findings highlight RPS20's dual roles as both a ribosomal component and a context-dependent regulator of cellular processes.