Centrinone (LCR-263) shows significant specificity, being over 1000 times more selective for Polo-like kinase 4 (Plk4) than for Aurora kinases A/B, and does not impact the phosphorylation of Aurora A or B substrates at doses that cause centrosome depletion. When administered to HeLa human cervical carcinoma cells, Centrinone (LCR-263) initiates a gradual decrease in the presence of centriolar and pericentriolar material markers with each cell division cycle, leading to most cells eventually lacking centrioles and centrosomes. This effect suggests Plk4's role in centriole duplication extends to differentiated cells, as seen in the reduced number of centrioles in multiciliated Xenopus epithelial cells. Centrinone (LCR-263) treatment results in the depletion of centrosomes across various vertebrate cell lines. The absence of centrosomes causes normal cells to enter an irreversible, senescence-like state during the G1 phase through a p53-dependent mechanism, which is notable for its independence from DNA damage, stress, Hippo pathway signaling, extended mitosis, or errors in chromosome segregation^[1].