ZC3H12B (also known as Regnase-2 or MCPIP2) is an RNA endonuclease that functions as a critical regulator of neuroinflammation and cellular proliferation 1. The protein contains a functional NYN/PIN RNase domain that mediates RNA degradation through direct binding to target mRNAs 2. ZC3H12B binds to the 3' untranslated regions (UTRs) of inflammatory cytokine mRNAs, including IL-6 and IL-1β, leading to their destabilization and reduced protein production 23. The protein is highly expressed in healthy brain tissue but becomes downregulated during neuroinflammation and glioblastoma progression 3. In glioblastoma cells, ZC3H12B acts as a tumor suppressor by targeting cell cycle-related transcripts including cyclins (CCND1, CCNE1, CCNE2, CCNA2, CCNB1, CCNB2) and mitosis regulators (AURKA, PLK1), resulting in G1 cell cycle arrest and inhibited proliferation 1. RNA-SELEX studies demonstrate that ZC3H12B binds structured RNA motifs through its PIN RNase domain rather than its conventional zinc finger domain 4. The protein forms cytoplasmic granule-like structures characteristic of mRNA turnover machinery and participates in a regulatory loop with Regnase-1 3. ZC3H12B expression has been associated with prognosis in both Alzheimer's disease and various cancers, suggesting broad clinical relevance 56.