RPS2 (ribosomal protein S2) is a structural component of the small ribosomal subunit (40S) essential for protein synthesis 1. As part of the 40S subunit, RPS2 participates in mRNA binding and translation initiation, while also playing roles in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly 1. RPS2 protein stability is tightly regulated through ubiquitin-mediated degradation; during ribosome-associated quality control (RQC), RPS2 is monoubiquitinated by the E3 ligase ZNF598 in response to ribosome collisions, and subsequently deubiquitinated by the G3BP1-family-USP10 complex to prevent lysosomal degradation 2. RPS2 is also subject to regulatory protein-protein interactions involving PDCD2 family proteins and PRMT3-mediated arginine methylation 3. Clinically, RPS2 dysregulation associates with multiple cancers: it is significantly upregulated in glioblastoma where RACK1 stabilizes RPS2 to promote NF-κB pathway activation and cell proliferation 4; hypomethylation and elevated RPS2 expression occur in hepatocellular carcinoma, supporting oncogenic functions 5; and RPS2 is a core component of a ribosome biogenesis signature predicting poor prognosis in clear cell renal cell carcinoma 6. Additionally, RPS2 expression is upregulated at the blood-brain barrier in Alzheimer's disease patients 7, and RPS2 represents a core gene associated with ischemic stroke pathology 8.