FBL encodes fibrillarin, an S-adenosyl-L-methionine-dependent methyltransferase with dual catalytic functions in ribosome biogenesis. The protein catalyzes site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA, with specificity provided by base-pairing guide RNAs, and also mediates 2'-O-methylation of U6 snRNAs in box C/D RNP complexes, a modification required for mRNA splicing fidelity. Additionally, FBL acts as a protein methyltransferase, modifying histone H2A at glutamine 105—a mark that impairs FACT complex binding at the 35S ribosomal DNA locus. The protein is an integral component of the small subunit processome, the first precursor of the eukaryotic small ribosomal subunit, where it coordinates with ribosome biogenesis factors and RNA chaperones to direct RNA folding, modifications, rearrangement, and selective degradation during nucleolar assembly. FBL is highly conserved evolutionarily, with human and yeast fibrillarin sharing 70% identity and functional complementarity. Clinically, autoantibodies targeting FBL are highly specific for systemic sclerosis and are associated with skeletal muscle disease and primary pulmonary arterial hypertension in this population. The gene's role in fundamental ribosome biogenesis connects it to broad disease categories including cancer and metabolic disorders, though specific pathogenic mechanisms in these contexts remain to be fully elucidated.