TNKS (tankyrase) is a poly-ADP-ribosyltransferase that regulates multiple cellular processes through protein modification. Its primary function involves Wnt signaling pathway activation, where TNKS mediates poly-ADP-ribosylation of AXIN1 and AXIN2, key components of the β-catenin destruction complex, leading to their RNF146-mediated ubiquitination and degradation 1. Beyond Wnt signaling, TNKS regulates telomere length through poly-ADP-ribosylation of TERF1 and contributes to centrosome maturation by modifying HEPACAM2/MIKI 2. TNKS also participates in vesicle trafficking and proteasome activation. Mechanistically, TNKS catalyzes protein poly-ADP-ribosylation and can generate free poly(ADP-ribose) molecules independent of protein attachment 3. Disease relevance extends to cancer, where EZH2-mediated TNKS suppression disrupts centrosomal function, promoting chr8 instability and metastasis in triple-negative breast cancer 2. TNKS also regulates hepatitis B virus cccDNA levels through Wnt/β-catenin signaling, suggesting therapeutic potential for HBV 4. Additionally, TNKS genetic polymorphisms interact with environmental carcinogen exposure to influence telomere damage in occupational settings 5. These multifaceted roles establish TNKS as a critical target for cancer therapeutics and potential viral infection treatments.