Cellular RNAs in eukaryotes undergo extensive posttranscriptional modifications, but as yet only a few RNA-modifying enzymes have been identified and characterized. Here we report on the cloning of FTSJ2, a novel human gene encoding a putative RNA methyltransferase. FTSJ2 shares significant sequence homology with FtsJ/RrmJ, a recently identified Escherichia coli 23S rRNA uridine-2'-O-methyltransferase. FTSJ2 belongs to a new family of evolutionarily conserved S-adenosylmethionine-binding proteins. The gene FTSJ2 is located on chromosome 7p22 between MAD1L1 and NUDT1. It is 8 kb in length, spanning three exons. Northern blot analysis revealed that the FTSJ2 transcripts are abundant in skeletal muscle, placenta, and heart, as well as in cancer cells. Immunofluorescence staining demonstrated that FTSJ2 protein localizes to the nucleolus. Our results suggest that FTSJ2 is likely a nucleolar RNA methyltransferase involved in eukaryotic RNA processing and modification.