Probable thioesterase PNKD (PNKD)

Probable thioesterase PNKD (PNKD) is a metallo-beta-lactamase domain-containing synaptic protein highly expressed in the human brain and associated with paroxysmal nonkinesiogenic dyskinesia, a genetic movement disorder[1][2][3][4]. It exists in several isoforms produced by alternative splicing, with the long isoform localized to pre-synaptic membranes and interacting specifically with active zone proteins RIM1 and RIM2, thereby modulating neurotransmitter release and synaptic exocytosis[3]. Mutations in PNKD are causative for familial paroxysmal nonkinesiogenic dyskinesia, and altered expression has been linked to multiple cancers where it may influence cell proliferation and tumor progression, possibly via pathways such as MEK/ERK and MLC2/FAK/AKT[1]. PNKD also shares homology with hydroxyacylglutathione hydrolase (HAGH), though its hydrolytic activity appears minimal, and may function in cellular detoxification. There is currently no evidence for approved drugs targeting PNKD; its roles as a diagnostic biomarker are established for both familial movement disorders and some cancers. The protein's modulation of neurotransmitter release and synaptic stability presents both therapeutic opportunity and challenges in targeting CNS disorders[1][2][3][4].

Other names

Paroxysmal nonkinesiogenic dyskinesia proteinKIAA1184MR1Myofibrillogenesis regulator 1Brain protein 17BRP17DYT8FPD1FKSG19TAHCCP2PKND1MR-1SPNKD1KIPP1184MGC31943DKFZp564N1362Trans-activated by hepatitis C virus core protein 2

Not established for drugs; mechanism for protein function is inhibition/modulation of synaptic exocytosis via interaction with synaptic active zone proteins RIM1 and RIM2