PLK2 (polo-like kinase 2) is a serine/threonine kinase with dual roles as both a tumor suppressor and pathological mediator depending on cellular context. As a tumor suppressor, PLK2 functions in cell cycle regulation, particularly in G1/S transition and centriole duplication 1. PLK2 can phosphorylate and inhibit TAp73, a p53 family tumor suppressor, at Ser48 within the TA domain, thereby preventing TAp73's anti-tumor activity in osteosarcoma cells 2. However, PLK2 also promotes pathological processes in neurodegenerative diseases. In Parkinson's disease models, PLK2 promotes α-synuclein (SNCA) aggregation and neurotoxicity by disrupting autophagic flux through phosphorylation of DCTN1 at S1098, which impairs autophagosome-lysosome fusion and prevents clearance of toxic protein aggregates 3. PLK2 expression is regulated by MEK1/2-ERK2 signaling, and MEK1/2 inhibitors can reduce pathological α-synuclein through PLK2 modulation 4. Additionally, PLK2 expression can be suppressed by histone demethylase KDM5B in EBV-associated cancers, where PLK2 acts as a tumor suppressor whose inhibition activates PI3K/AKT/mTOR signaling 5. PLK2 can also be induced to promote cancer cell pyroptosis through USP18 inhibition 6.