RPS17 encodes a structural component of the small ribosomal subunit (40S) essential for protein synthesis 1. RPS17 functions as part of the small subunit (SSU) processome during ribosome biogenesis, where it associates with nascent pre-rRNA to facilitate RNA folding, modifications, and processing in the nucleolus 2. Beyond its canonical ribosomal role, RPS17 regulates osteoclast-precursor development and immune homeostasis; RPS17-dependent ribosome synthesis is essential for monocyte differentiation toward osteoclast-lineage fates, with RPS17 underexpression contributing to ankylosing spondylitis pathogenesis 3. RPS17 haploinsufficiency causes Diamond-Blackfan Anemia (DBA4), a rare congenital disorder characterized by selective erythroid aplasia and macrocytic anemia 4. RPS17 mutations impair erythropoiesis through reduced ribosomal protein synthesis, with downstream effects including downregulation of SLC4A1, a critical erythrocyte membrane protein 5. RPS17 mutations represent approximately 3-7% of genetically characterized DBA cases 6. DNA methylation episignature analysis demonstrates RPS17 mutations produce distinctive epigenetic biomarkers, establishing methylation profiling as a robust diagnostic tool for DBA 7. RPS17 has been validated as a reliable housekeeping gene for gene expression studies in normal and pathological ovarian tissues 8.