Dystonia is a debilitating movement disorder characterized by abnormal movements and postures. Given the absence of structural lesions in the brain of most dystonic patients, disruption of synaptic function has been long hypothesized to play a pivotal role in dystonia pathogenesis. We recently identified homozygous frameshift, nonsense, and missense variants in TSPOAP1, the gene encoding active zone RIM-binding protein 1 (RIMBP1), as a novel genetic cause of autosomal recessive dystonia (Mencacci et al., JCI, 2021). RIMBP1 is a presynaptic protein that localizes voltage-gated Ca2+ channels (VGCCs) and Ca2+ activated potassium channels (BKs) to the active zone, ensuring tight coupling between presynaptic spikes and vesicle exocytosis. In our latest work, we aim to unravel how RIMBP1 pathogenic variants impact synaptic transmission and cause dystonia. For this, we first reprogrammed fibroblasts from patients with dystonia carrying bi-allelic TSPOAP1 homozygous variants into induced pluripotent stem-cells (iPSCs). Then we used CRISPR/Cas9 homology-directed repair technology to correct these variants, generating isogenic control lines. Finally, we derived isogenic mutant and control iPSCs into functional induced human neurons, and assessed in detail their morphology and function using confocal and stimulated emission depletion (STED) microscopy, micro-electrode array technology, and patch clamp electrophysiology. Our preliminary data showed that RIMBP1 pathogenic variants affect neural network activity and synaptic puncta abundance and distribution along dendrites. In conclusion, we expect to uncover convergent presynaptic abnormalities triggered by all currently described dystonia-causing TSPOAP1 variants, which can then be corrected using genetic and pharmacological approaches.