ZC3H12C (zinc finger CCCH-type containing 12C), also known as MCPIP3 or Regnase-3, is an RNA-binding endoribonuclease that regulates post-transcriptional gene expression through mRNA destabilization and alternative splicing. The protein contains both PIN and CCCH zinc finger domains that cooperatively recognize and bind single-stranded RNA substrates, with the zinc finger showing unique structural features for trinucleotide sequence recognition 1. In macrophages, ZC3H12C suppresses pro-inflammatory macrophage activation by modulating STAT1 alternative splicing and restricting TNF-α and IL-6 production through inhibition of NF-κB and MAPK signaling pathways 23. In endothelial cells, ZC3H12C similarly attenuates TNFα-induced chemokine and adhesion molecule expression by suppressing NF-κB signaling 4. In keratinocytes, ZC3H12C regulates epidermal proliferation and differentiation by directly cleaving cyclin B1 mRNA within its 3'-UTR 5. Additionally, ZC3H12C and regnase-1 collaborate to control hematopoietic stem cell lineage decisions by regulating Nfkbiz mRNA degradation, promoting lymphoid over myeloid differentiation 6. Dysregulation of ZC3H12C is associated with chr11 inflammatory diseases including psoriasis 7 and pediatric acute myeloid leukemia relapse 8, making it clinically relevant as both a therapeutic target and prognostic marker.