RO60 is an RNA-binding protein that functions as a core component of nucleocytoplasmic ribonucleoprotein complexes essential for RNA metabolism and cellular homeostasis 1. RO60 stabilizes and mediates quality control of small RNAs, including Y RNAs, retroelement transcripts, and misfolded RNAs 1. The protein binds endogenous Alu retroelements that are induced by type I interferon and regulate inflammatory gene expression 2. RO60 deletion enhances Alu RNA and interferon-regulated gene expression, linking the protein to interferon pathway regulation 2. Loss of RO60 function or transcriptional dysregulation generates small RNA fragments that activate inflammatory cascades through endosomal toll-like receptors and cytoplasmic RNA sensors, triggering autoreactive B cell responses 1. Clinically, anti-RO60 autoantibodies serve as diagnostic markers for Sjögren's disease and systemic lupus erythematosus 1. Anti-RO60 positivity in SLE patients is associated with higher disease activity, hypocomplementemia, and increased immunosuppressive treatment requirements 3. Combined anti-RO52/RO60 antibody positivity correlates with increased disease severity in Sjögren's disease through potentiated interferon pathway activation 4.