Mutations in TMEM151A, an almost unknown gene, have been recently found in Paroxysmal Kinesigenic Dyskinesia (PKD), an autosomal dominant movement disorder and in few cases of Benign Familial Infantile Epilepsy (BFIE). The major gene associated to PKD and BFIE is PRRT2. Interestingly, the drug treatment of choice for PKD caused by TMEM151A or PRRT2 mutations is Carbamazepine, a sodium channel blocker. Indeed, PRRT2 has been shown to control neuronal excitability by modulating voltage gated sodium channels. Both PRRT2 and TMEM151A are membrane associated proteins expressed in the nervous system. To gain insight on TMEM151A function we investigated the effects of some pathological mutations of TMEM151A by in vitro assays, and we show that they frequently cause alteration in the protein expression, suggesting a possible loss of function mechanism, similarly to what frequently happens with PRRT2 pathological variants.Therefore, our hypothesis is that PRRT2 and TMEM151A could share similar pathophysiological mechanisms. To address this point, we are studying TMEM151A topology and expression as well as its role in neuronal development and excitability. To gain insight on TMEM151A membrane topology, we started from in-silico 3D modelling simulations of the protein structure and validated the modelling by live-labelling immunofluorescence and electron microscopy assays.This may help to understand the physio-pathological mechanisms at the basis of these paroxysmal disorders and to get a step forward for the identification of new targeted therapeutic strategies.