ERI3 (ERI1 exoribonuclease family member 3) is an RNA-binding protein with 3'-5' exonuclease activity localized to the cytosol and Golgi apparatus 1. Its primary function involves exonucleolytic trimming to generate the mature 3' end of 5.8S rRNA from tricistronic rRNA transcripts, supporting ribosome biogenesis 2. ERI3 negatively regulates regulatory ncRNA-mediated heterochromatin formation and plays a conserved role in Flavivirus replication, where it associates with dengue viral RNA via 3' UTR interactions and is required for viral RNA synthesis 1. Clinically, ERI3 demonstrates significant disease relevance across multiple conditions. In hepatocellular carcinoma, ERI3 is significantly overexpressed and serves as an independent prognostic factor, with high expression correlating with reduced overall survival (HR=2.86) and enhanced cell proliferation, migration, and invasion 34. In ischaemic stroke, ERI3 is part of a 12-gene ribosome biogenesis signature that assesses prognostic risk and associates with immune infiltration patterns 2. Additionally, ERI3 DNA methylation (cg13451048) is associated with insulin resistance (HOMA2-IR) and glycated hemoglobin (HbA1c) in older adults, suggesting involvement in metabolic regulation 5. L1 retrotransposon insertions within ERI3 have been associated with schizophrenia pathogenesis 6.