PDE12 is a poly(A)-specific exoribonuclease with dual roles in antiviral immunity and mitochondrial RNA processing. Primary function: PDE12 cleaves both 2',5'- and 3',5'-phosphodiester bonds in oligoadenylates 12, serving as a negative regulator of the interferon-induced 2-5A system 3. Mechanism: PDE12 degrades 2',5'-oligoadenylate units, reducing RNAseL activation and decreasing antiviral responses 3. In mitochondria, PDE12 removes poly(A) tails from mitochondrial mRNAs, regulating translation efficiency and steady-state transcript levels 2. Disease relevance: PDE12 inhibition enhances antiviral activity against multiple RNA viruses including SARS-CoV-2, HCV, dengue, and West Nile virus 3. Conversely, pathogenic PDE12 variants cause neonatal mitochondrial disease with respiratory chain deficiencies, lactic acidosis, and neurological/muscular phenotypes due to impaired mitochondrial RNA processing 45. Clinical significance: Decreased PDE12 expression associates with recently diagnosed type 1 diabetes 6, and PDE12 promotes gastric cancer progression via TCAF2/JAK2/STAT3 axis activation 7. PDE12 inhibitors show therapeutic potential as pan-RNA virus antivirals 3.