DDX54 is a nucleolar DEAD-box RNA helicase with pleiotropic cellular functions. Primarily, it plays an essential role in ribosome biogenesis by remodeling rRNA structure and initiating peptidyl transferase center formation 1. DDX54 regulates transcriptome dynamics during DNA damage response by enhancing splicing efficacy of IR-induced pre-mRNAs containing weak acceptor splice sites through interaction with U2 snRNP and spliceosomal B complex components 2. Additionally, DDX54 functions as a nucleotide exchange factor for casein kinase 2, stimulating its enzymatic activity 3. Immunologically, DDX54 acts as an inhibitor of type I interferon antiviral response. Upon viral infection, DDX54 relocates from nucleolus to nucleoplasm where it facilitates ALKBH5-mediated m6A demethylation of antiviral transcripts including mavs mRNA, thereby impairing interferon response and promoting viral replication 4. In the nervous system, DDX54 contributes to CNS myelination, with knockdown studies showing impaired myelin basic protein accumulation and disrupted axonal myelination in the corpus callosum 5. Clinically, DDX54 downregulation enhances anti-PD1 immunotherapy responsiveness in immune-desert lung tumors with high tumor mutational burden by increasing immune cell infiltration 6. Notably, differentially expressed circRNAs binding to DDX54 were identified as potential diagnostic markers in schizophrenia 7.