RPS4Y1 (ribosomal protein S4 Y-linked 1) is a Y-chrY-encoded structural component of the cytosolic small ribosomal subunit involved in translation 1. Beyond its canonical ribosomal function, RPS4Y1 exhibits disease-relevant roles in multiple pathological contexts. In endothelial cells, high glucose upregulates RPS4Y1, which promotes apoptosis and inflammation through p38 MAPK pathway activation, implicating it in diabetic complications 1. RPS4Y1 shows sex-specific expression in ulcerative colitis, where it is significantly upregulated in males and correlates with differential immune cell infiltration and macrophage function 2. The gene displays altered expression across several inflammatory and neoplastic conditions: downregulation in COPD monocytes/macrophages 3, identification as a hub gene in traumatic brain injury with diagnostic value in serum 4, and a prominent role in a machine learning model predicting lymph node metastasis in papillary thyroid carcinoma with AUROC of 0.911-0.953 5. In pancreatic cancer, RPS4Y1+ tumor cell subsets contribute significantly to immunosuppressive microenvironments 6. Additionally, RPS4Y1 was identified as a common differentially expressed gene in Alzheimer's disease and major depressive disorder dorsolateral prefrontal cortex 7. These findings suggest RPS4Y1 functions beyond translation, potentially serving as a biomarker for disease diagnosis and prognosis across multiple clinical contexts.