RPL39 encodes ribosomal protein L39, a structural component of the large ribosomal subunit essential for protein synthesis 1. Beyond its canonical ribosomal function, RPL39 exhibits significant oncogenic properties across multiple cancer types. In breast cancer, RPL39 promotes tumor initiation and metastasis through nitric oxide synthase (NOS) signaling pathways 2. A gain-of-function mutation (A14V) occurs in 97.5% of metaplastic breast cancers and correlates with reduced patient survival 3. The protein's oncogenic effects are mediated through inducible NOS signaling driven by RNA editing enzyme ADAR1 3. RPL39 also promotes cancer cell proliferation, migration, and invasion in pancreatic cancer 4, gliomas 5, and affects trophoblast cell behavior in preeclampsia 6. Mechanistically, RPL39 influences cell cycle progression, apoptosis resistance, and epithelial-mesenchymal transition markers like E-cadherin 6. Recent studies reveal RPL39's role in macrophage proliferation and sex differences in pulmonary arterial hypertension 7. The protein paralog RPL39L demonstrates specialized functions in cotranslational folding of alpha-helical domains, particularly in pluripotent cells 1. These findings establish RPL39 as both a fundamental ribosomal component and a significant therapeutic target in multiple diseases.