The function of DDX54 (DEAD-box helicase 54, ENSG00000123064) is as follows. Nucleolar RNA helicase that is involved in diverse cellular processes including ribosome biogenesis, DNA damage response, RNA splicing, transcriptional regulation, innate immunity, and nervous system development. Plays an essential role in the formation of the ribosome active site by remodeling rRNA structure and initiating peptidyl transferase center formation (PubMed:38632236). Represses the transcriptional activity of several nuclear receptors. Regulates transcriptome dynamics during DNA damage response. Mechanistically, acts via increased interaction with a well-defined class of pre-mRNAs that contain introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex. These activities lead to reduced intron retention and enhanced processing rates of its target transcripts (PubMed:28596291). Acts as an inhibitor of type I interferon antiviral response by facilitating ALKBH5-mediated demethylation of specific transcripts (PubMed:40793791). Contributes to central nervous system myelination, likely through regulation of oligodendrocyte differentiation and myelin sheath formation (By similarity). {ECO:0000250|UniProtKB:Q8K4L0, ECO:0000269|PubMed:12466272, ECO:0000269|PubMed:28596291, ECO:0000269|PubMed:38632236, ECO:0000269|PubMed:40793791}.