PLK4 is a serine/threonine kinase that serves as the master regulator of centriole duplication, orchestrating the formation of procentrioles on parental centrioles through recruitment of essential biogenesis proteins including SASS6, CPAP, and CEP135 1. The kinase localizes to centrosomes, nucleolus, and cleavage furrow, with expression increasing through S and M phases before APC/C-dependent degradation 2. PLK4 phosphorylates multiple substrates including FBXW5, STIL, CEP131, and PCM1, regulating centriolar satellite organization and centriole replication fidelity 3. Beyond centriole biology, PLK4 participates in deuterosome-mediated centriole amplification in multiciliated cells and trophoblast differentiation through HAND1 phosphorylation. Clinically, PLK4 deregulation drives tumorigenesis and genomic instability, with overexpression associated with advanced disease and poor outcomes across multiple cancer types 4. Haploinsufficient PLK4 mice show tumor predisposition with spontaneous liver tumors and multipolar spindles during hepatocyte proliferation 2. PLK4 inhibition represents a promising therapeutic strategy, particularly for neuroblastoma and breast cancer with 17q amplification, where TRIM37 levels determine mitotic vulnerability 5. Recent CRISPR screens identify PLK4 as a target to overcome oxaliplatin resistance in colorectal cancer 6, with clinical trials underway exploring single-agent and combination approaches.