ERI1 is a 3'-to-5' exoribonuclease that catalyzes degradation of histone mRNAs after DNA replication and processes the 3' end of 5.8S ribosomal RNA. The enzyme binds with high affinity to the stem-loop structure of histone pre-mRNAs and requires the 5'-ACCCA-3' sequence for efficient activity. ERI1-mediated RNA metabolism also regulates small interfering RNAs and contributes to epigenetic gene regulation through modulation of RNA interference pathways 1. In chondrogenesis and skeletal development, ERI1 function is particularly critical: missense variants cause loss of exoribonuclease activity, leading to defective 5.8S rRNA trimming and impaired histone mRNA degradation, which manifests as severe spondyloepimetaphyseal dysplasia in affected individuals 2. Conversely, biallelic null variants present with milder phenotypes including mild intellectual disability and digital anomalies 23. During influenza A virus infection, ERI1 is co-opted by viral ribonucleoproteins to promote viral transcription, indicating that its RNA-binding and catalytic activities support both cellular and pathogenic RNA metabolism 4. Emerging evidence suggests ERI1 variants may contribute to cardiometabolic disease susceptibility through effects on atherosclerosis and shared genetic pathways with type 2 diabetes and depression 56.