RPL15 is a structural component of the cytosolic large (60S) ribosomal subunit essential for protein synthesis 1. As an RNA-binding protein, RPL15 participates in translation initiation and selectively regulates synthesis of ribosomal proteins and cell cycle regulators 1. Beyond its canonical ribosomal function, RPL15 expression is dynamically regulated across multiple physiological and pathological contexts. During erythropoiesis, RPL15 upregulation due to decreased DNA methylation triggers endoplasmic reticulum stress and unfolded protein response activation, affecting terminal erythroid differentiation 2. In cancer biology, RPL15 shows context-dependent roles: overexpression promotes breast cancer metastasis by enhancing translation of proliferation factors 1, while downregulation associates with poor prognosis in pancreatic ductal adenocarcinoma through epithelial-mesenchymal transition 3. Notably, RPL15 is a therapeutic target—selective RPL15 degradation via PROTAC technology enhances anti-PD-1 immunotherapy efficacy by inducing DAMP secretion and cGAS-STING activation 4. Decreased RPL15 expression exacerbates aortic valve calcification 5, and RPL15 upregulation is implicated in Alzheimer's disease pathology at the blood-brain barrier 6. Mutations in RPL15 cause Diamond-Blackfan anemia through impaired ribosome biogenesis and elevated TP53-mediated apoptosis 7.