Proline-rich transmembrane protein 2 (PRRT2)

Proline-rich transmembrane protein 2 (PRRT2) is a neuron-specific, type II transmembrane protein encoded by the PRRT2 gene on chromosome 16[2][3]. Its structure comprises an intracellular proline-rich N-terminal domain, a helix–loop–helix motif forming the first “transmembrane” domain (actually cytoplasmic), a genuine membrane-spanning C-terminal domain, and a very short extracellular tail[1][3]. PRRT2 is a key regulator of neuronal excitability: it interacts with and modulates voltage-gated sodium channels (Nav1.2 and Nav1.6), affecting their surface localization and biophysical properties, which is critical to the generation and propagation of action potentials in neurons[1][4]. It also interacts with synaptic proteins such as SNAP-25, VAMP1, syntaxin 1B, and intersectin 1, thereby participating in synaptic vesicle cycling and neurotransmitter release[4][5]. Loss-of-function mutations in PRRT2 cause a spectrum of pleiotropic, paroxysmal neurological syndromes of infancy and childhood, including paroxysmal kinesigenic dyskinesia, benign familial infantile convulsions, episodic ataxia, and certain forms of migraine[2][3][4]. No therapies currently exist that target PRRT2 directly, but diagnosis and genetic testing for PRRT2 mutations are well-established clinical tools[2][3].

Other names

Dispanin subfamily B member 3DSPB3IFITMD1FICCAEKD1PKCFLJ25513DKFZp547J199BFIC2BFIS2DYT10ICCAParoxysmal kinesigenic dyskinesiaBenign familial infantile convulsions-2Infantile convulsions and paroxysmal choreoathetosisEpisodic kinesigenic dyskinesia 1interferon induced transmembrane protein domain containing 1

Not applicable (no direct PRRT2-targeted therapeutics known)[2][3][4].