RRP8 encodes a nucleolar ribosomal RNA processing protein that functions as an N1-methyladenosine (m1A) methyltransferase targeting specific adenine residues in large subunit ribosomal RNA 1. The protein catalyzes m1A modification at conserved positions across species, including A674 in C. elegans 26S rRNA, corresponding to equivalent sites in yeast 25S and human 28S rRNA 1. Beyond ribosomal RNA modification, RRP8 serves as an essential component of the energy-dependent nucleolar silencing (eNoSC) complex, where it acts as an H3K9me2 reader and probable methyltransferase in response to glucose starvation and cellular energy status. In disease contexts, RRP8 demonstrates significant clinical relevance as an autoantigen in lupus nephritis, where anti-RRP8 antibodies are found in 63.6% of patients with nephritis compared to only 12.5% without nephritis 2. The protein shows upregulated expression across multiple cancer types and correlates with poor prognosis, tumor heterogeneity, and immune cell infiltration 34. In hepatocellular carcinoma, RRP8 promotes cell proliferation and migration through MEK1/2 and β-catenin signaling pathways 4. Additionally, RRP8 expression is associated with podocyte mitotic catastrophe in kidney diseases and shows activation during acute multiple sclerosis relapses 56.