TNKS2 (tankyrase 2) is a poly-ADP-ribosyltransferase with pleiotropic cellular functions. Primary function involves positive regulation of canonical Wnt/β-catenin signaling through poly-ADP-ribosylation of AXIN1 and AXIN2, key components of the β-catenin destruction complex 12. RNF146 recognizes these poly-ADP-ribosylated proteins and mediates their ubiquitination and degradation, thereby activating Wnt signaling. TNKS2 also contributes to telomere regulation through poly-ADP-ribosylation of TERF1 3 and stimulates 26S proteasome activity 4. In disease contexts, TNKS2 dysregulation contributes to multiple pathologies. In cervical cancer, miR-20a-mediated upregulation of TNKS2 promotes cellular proliferation, migration, and invasion 5. Conversely, in colorectal cancer, miR-582-5p targeting of TNKS2 inhibits migration and chemo-resistance 6. TNKS2 also plays roles in melanocyte stem cell maintenance through interaction with SASH1 7, and genetic polymorphisms in TNKS2 associate with laryngeal squamous cell carcinoma risk 8. During influenza A virus infection, TNKS2 elevation promotes viral replication, and miR-206-mediated TNKS2 suppression enhances antiviral responses 9. In tuberculosis, TNKS2 downregulation via the miR-582-5p axis induces macrophage autophagy 10. These findings establish TNKS2 as a multi-functional enzyme with significant therapeutic targeting potential.