My research focuses on unravelling the molecular basis of hereditary ataxias, motor neuron diseases and dementias, identifying translational biomarkers, and preparing targeted treatments for these fascinating complex neurodegenerative diseases. I have a broad research and clinical background with specific training and expertise in next-generation genomics, deep-phenotyping, and translational studies, with now >250 PubMed listed peer-reviewed publications on these neurogenetic conditions. As PI or co-PI of several global consortia (e.g. PREPARE, GENFI, DZNE FTD, EarlyOnset-Ataxia Network) as well as of manifold university- and extra-mural grants, I laid the groundwork for the proposed research by running several international, collaborative genomic studies in all of the aforementioned disease groups. In particular, the combination of deep-phenotyping of worldwide cohorts together with next-generation genomics has allowed us to unravel the genetic cause of >15 genetically undefined ataxia and spasticity syndromes, identifying novel ataxia or spastic paraplegia genes or mutational mechanisms e.g. for PNPLA6, WWOX, OPA1, DNJAC3 or SERAC1. Following the launch of the German Early-Onset Ataxia Network (5 main German ataxia sites) in 2013, I have been leading the EU-funded global PREPARE consortium “Preparing therapies for autosomal-recessive ataxias”, which unites European and Canadian centers to a common network to prepare molecular therapies for ARCAs, and which has subsequently been joined by partners from all over the world (2020: 31 sites total). As part of this unique global collaborative effort for ARCAs, we have now aggregated >1100 patient visits in a shared web-based longitudinal global ARCA registry, >800 biosamples from ARCA patients in a shared ARCA biobank, and >1500 ataxia NGS datasets in the collaborative Miami-based GENESIS platform. These large international ARCA networks and datasets of collaborative partners have now become the basis for the “ATAXIA GLOBAL” initiative - a worldwide multicenter translational initiative to pave the way for all crucial translational steps from NGS genetic fingerprinting to FDA-conform trial-readiness cohorts of ARCA patients, as outlined in our recent NEURON review (Synofzik et al., 2019). The current application perfectly extends this large-scale endeavour and can directly draw on these global patient, biomaterial and NGS datasets.