Superiority of PLK-2 as α-synuclein phosphorylating agent relies on unique specificity determinants

► α-Synuclein S129 is readily phosphorylated in vitro by PLK-2 and -3, not by CK2. ► S129 phosphorylation by PLK2 is relying on the consensus E-x-x-S-x-E. ► PLK2 targeting α-synuclein is dictated both by local and remote determinants.