PCBP1 (poly(rC) binding protein 1) is a multifunctional RNA and single-stranded DNA binding protein with roles spanning viral infection, transcriptional regulation, and iron homeostasis. Functionally, PCBP1 acts as an iron chaperone that loads iron to ferritins and maintains intracellular iron homeostasis 12. During poliovirus infection, PCBP1 facilitates viral RNA replication initiation in concert with viral protein 3CD [UniProt annotation]. Beyond infection, PCBP1 regulates transcription by recruiting the G-quadruplex helicase DHX9 to promoter regions, modulating R-loop processing and transcription of target genes 3. PCBP1 also functions as an adaptor protein in the NAT10/PCBP/TDP43 complex, mediating mRNA ac4C acetylation through substrate selection and tethering 4. In disease contexts, PCBP1 dysregulation has significant clinical implications. PCBP1 mutations occur in genome-stable colorectal and gastric adenocarcinomas 5. Notably, PCBP1 represses ferroptosis in head and neck cancer by inhibiting ferritinophagy through direct binding to BECN1 mRNA 1. In colorectal cancer, PCBP1 downregulation by ferroptosis inducers promotes iron accumulation and cell death 6. Conversely, PCBP1 protects against metabolic dysfunction-associated steatotic liver disease by maintaining iron homeostasis and suppressing lipid peroxidation 2. These contrasting roles suggest context-dependent functions where PCBP1 modulation represents a therapeutic strategy in both cancer and metabolic disease.