NOP2 is a S-adenosyl-L-methionine-dependent methyltransferase that catalyzes 5-methylcytosine (m5C) modification of ribosomal RNA, specifically methylating cytosine 4447 in 28S rRNA 1. The protein is essential for efficient rRNA processing and 60S ribosomal subunit biogenesis 23, functioning through non-catalytic complex formation with box C/D snoRNAs to facilitate recruitment and stable assembly of U3 and U8 snoRNAs into pre-90S ribosomal particles 3. Beyond ribosomal functions, NOP2 participates in cell cycle regulation and nucleolar activity associated with cell proliferation 2. In disease contexts, NOP2 (also called NSUN2 in related literature) plays significant roles in cancer progression. Aberrant m5C hypermethylation mediated by NSUN2 contributes to gefitinib resistance in EGFR-mutant lung cancer through the NSUN2-YBX1 axis 4, and promotes colorectal cancer progression via m5C-dependent stabilization of oncogenic transcripts 5. Additionally, mitochondrial m5C modifications dependent on NOP2 family members are critical for metabolic plasticity driving metastasis 6. NOP2 has been identified as a diagnostic biomarker for sepsis 7, and m5C RNA modifications catalyzed by NOP2 family methyltransferases regulate RNA stability, translation, and expression of multiple oncogenes 89.