PLK5

PLK5 (Polo-like kinase 5) is the most divergent member of the polo-like kinase family and is primarily associated with cellular stress responses, cell-cycle regulation, and neuronal differentiation rather than canonical mitotic control pathways dominated by other PLK isoforms^[1][2]. Mechanistically, PLK5 shares greater sequence similarity with PLK2 and PLK3 than with PLK1 or PLK4, and its expression is induced by DNA damage and other cellular stressors, linking PLK5 to DNA damage response signaling and maintenance of cellular integrity^[1][2]. Experimental studies demonstrated that murine PLK5 localizes predominantly to the nucleolus, where it is proposed to participate in stress-associated regulatory processes, and ectopic PLK5 expression induces G₁ arrest, reduced DNA synthesis, and apoptosis^[2]. In disease-related contexts, PLK5 has been implicated as a tumor-suppressive factor in glioblastoma, and silencing of the human PLK5 gene through promoter hypermethylation has been reported in astrocytoma and glioblastoma multiforme^[3]. Additional clinical evidence indicates that reduced PLK5 expression is associated with advanced tumor characteristics and unfavorable prognosis in non-small cell lung cancer, supporting a broader role in cancer biology^[4]. Compared with related PLK isoforms, human PLK5 is distinguished by a premature stop codon that truncates part of the kinase domain, producing a protein with markedly reduced catalytic potential while retaining biological activity in cellular stress responses and checkpoint regulation^[2]. Unlike PLK1-targeted therapeutic strategies, no selective PLK5 agonists or inhibitors have been established, and current research applications primarily employ genetic manipulation and expression analyses to investigate PLK5-mediated regulation of stress signaling, neuronal differentiation, and tumor suppression^[2][3].