This study demonstrates the use of patient-specific induced pluripotent stem cells (iPSCs) to model familial dysautonomia (FD), a rare and fatal peripheral neuropathy caused by a mutation in the IKBKAP gene. The researchers derived FD-iPSCs from patient fibroblasts and differentiated them into cells of all three germ layers, including peripheral neurons. Gene expression analysis revealed tissue-specific mis-splicing of IKBKAP in FD-iPSCs, suggesting a mechanism for disease specificity. Further analysis showed defects in neurogenic differentiation and migration behavior in FD-iPSCs. The study also validated the potency of candidate drugs, such as kinetin, in reversing aberrant splicing and ameliorating neuronal differentiation and migration in FD-iPSCs. These findings highlight the potential of iPSC technology for gaining novel insights into human disease pathogenesis and treatment. The study also provides a powerful model system to probe disease pathogenesis and validate candidate drugs. The results demonstrate that FD-iPSCs can be used to model the disease and test potential therapies. The study also shows that FD-iPSCs can be used to explore the molecular mechanisms underlying the disease and to identify and validate candidate drugs. The study also highlights the importance of iPSC technology in drug discovery and disease modeling. The study provides a comprehensive understanding of FD pathogenesis and the potential of iPSC technology in disease research.This study demonstrates the use of patient-specific induced pluripotent stem cells (iPSCs) to model familial dysautonomia (FD), a rare and fatal peripheral neuropathy caused by a mutation in the IKBKAP gene. The researchers derived FD-iPSCs from patient fibroblasts and differentiated them into cells of all three germ layers, including peripheral neurons. Gene expression analysis revealed tissue-specific mis-splicing of IKBKAP in FD-iPSCs, suggesting a mechanism for disease specificity. Further analysis showed defects in neurogenic differentiation and migration behavior in FD-iPSCs. The study also validated the potency of candidate drugs, such as kinetin, in reversing aberrant splicing and ameliorating neuronal differentiation and migration in FD-iPSCs. These findings highlight the potential of iPSC technology for gaining novel insights into human disease pathogenesis and treatment. The study also provides a powerful model system to probe disease pathogenesis and validate candidate drugs. The results demonstrate that FD-iPSCs can be used to model the disease and test potential therapies. The study also shows that FD-iPSCs can be used to explore the molecular mechanisms underlying the disease and to identify and validate candidate drugs. The study also highlights the importance of iPSC technology in drug discovery and disease modeling. The study provides a comprehensive understanding of FD pathogenesis and the potential of iPSC technology in disease research.