FBLL1 (fibrillarin like rRNA 2'-O-methyltransferase 1) is an S-adenosyl-L-methionine-dependent RNA 2'-O-methyltransferase that catalyzes 2'-hydroxyl ribose methylation in RNAs as part of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes 1. Unlike fibrillarin (FBL), the only previously known snoRNP 2'-O-methyltransferase, FBLL1 exhibits distinct site selectivity and tissue-specific distribution, being preferentially expressed in the brain 1. In neurons, FBLL1 promotes neuronal differentiation through 2'-O-methylation of GAP43 mRNA, stabilizing its expression; knockdown of FBLL1 reduces GAP43 methylation and impairs neuronal differentiation 1. Beyond its neuronal role, FBLL1 demonstrates broader disease relevance in cancer. It functions as a ribosome biogenesis-related gene with prognostic significance in prostate cancer, where upregulation correlates with poor outcomes 2. In hepatocellular carcinoma (HCC), FBLL1 is significantly upregulated and serves as an independent prognostic marker [PMID:33297932; 3; 43]. Mechanistically, FBLL1 promotes HCC malignant transformation through EGFR-MAPK pathway activation in conjunction with c-Myc upregulation 5. Functionally, FBLL1 knockdown inhibits HCC cell proliferation and clonogenic capacity, while overexpression promotes tumorigenic phenotypes in xenograft models 5, positioning FBLL1 as a promising therapeutic target in liver cancer.