PLK4

PLK4 (Polo-like kinase 4) is a serine/threonine kinase that functions as the master regulator of centriole duplication and initiates procentriole assembly at the mother centriole, thereby maintaining centrosome homeostasis during the cell cycle^[1][2][3]. Mechanistically, PLK4 controls the earliest steps of centriole biogenesis through kinase-dependent signaling and phosphorylation events that promote recruitment of centriole assembly factors, including the STIL-SAS6 module required for procentriole formation^[4][5]. Autophosphorylation further regulates PLK4 spatial organization and activity, enabling the establishment of a single centriole assembly site and restricting centriole duplication to once per cell cycle^[5][6]. Dysregulation of PLK4 expression disrupts centrosome number control; PLK4 overexpression induces centrosome amplification, whereas PLK4 depletion or kinase inhibition prevents procentriole formation and can lead to centrosome loss^[2][3][5]. In disease settings, elevated PLK4 expression has been reported in multiple human cancers and is associated with centrosome amplification, chromosomal instability, tumor progression, and adverse clinical outcomes^[7][8]. Compared with other Polo-like kinase family members, PLK4 is distinguished by its specialized role in centriole duplication rather than broader regulation of mitotic progression, making it a unique regulator of centrosome biogenesis^[2][9]. For experimental applications, selective PLK4 inhibitors such as centrinone enable reversible centriole depletion and provide widely used tools for investigating centrosome biology, cell-cycle surveillance pathways, and therapeutic vulnerabilities associated with aberrant centrosome number^[10][11].