The insights gained from the identification of RNU4-2 as a causative gene for neurodevelopmental disorders underscore the potential for discovering additional non-coding genetic contributors to a wide range of complex diseases. The study highlights the critical role of non-coding RNAs, such as RNU4-2, in regulating essential cellular processes and their implication in disease pathogenesis. By demonstrating the impact of non-coding variants on splicing regulation and neurodevelopment, this research sets a precedent for exploring the involvement of non-coding elements in other complex diseases beyond NDD. The systematic disruption of splice site usage observed in individuals with RNU4-2 variants suggests a broader relevance of non-coding RNAs in modulating gene expression and cellular functions. Therefore, the findings from this study could pave the way for uncovering additional non-coding genetic contributors to diverse complex diseases, offering new insights into disease mechanisms and potential therapeutic targets.