Although preventing or mimicking serine-129 phosphorylation does not alter the rate of cell death of Lewy inclusion-bearing neurons in vivo, PLK2 genetic deletion does provide relative protection from cell death of these vulnerable neurons, and selective pharmacologic inhibition of PLK2 may represent a promising strategy for modifying disease progression in PD, DLB, and related disorders. This evidence concerns the gene PLK2 and Lewy body dementia.