ERI1 is a conserved 3'-to-5' exoribonuclease with critical roles in RNA metabolism and skeletal development. Its primary function involves binding to the stem-loop structure of replication-dependent histone pre-mRNAs 12 and catalyzing their degradation after DNA replication 3. ERI1 also catalyzes the final trimming step in 5.8S rRNA 3' end processing, localizing to the nucleolus and associating with ribosomes 4. The enzyme recognizes a 5'-ACCCA-3' sequence within histone mRNA stem-loops 1 and requires 2' and 3'-hydroxyl groups on the last nucleotide for efficient degradation 1. Additionally, ERI1 regulates RNA interference by degrading siRNA 3'-overhangs 5. Pathogenic ERI1 variants cause a phenotypic dichotomy in skeletal development: missense mutations result in severe spondyloepimetaphyseal dysplasia with impaired 5.8S rRNA trimming and histone mRNA degradation, while null variants produce only mild intellectual disability and digital anomalies 3. Patient-derived iPSCs with missense variants show defective chondrogenesis 3. ERI1's functions extend to viral pathogenesis, where influenza A virus co-opts the ERI1-histone mRNA processing complex to promote viral transcription 6. These findings establish ERI1 as a critical regulator of skeletal patterning and a hub protein in diverse RNA metabolic pathways.