Glancing at TTI2’s role in the context of Autosomal Recessive Intellectual Developmental disorder

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Intellectual disability (ID) affects approximately 2–3% of the global population and typically manifests during childhood, leading to deficits in cognitive function and social interaction. As with other neurodevelopmental disorders, ID is characterized by dysregulation of neuronal physiology, including aberrant synapse formation, function, and plasticity, which contribute to the characteristic behavioural phenotype. Although the prevalence of rare diseases, including ID, is relatively low, their collective impact on patients' quality of life and the associated societal burden is substantial. Therefore, advancing scientific research is essential to elucidate the pathophysiological mechanisms underlying these disorders and to identify potential therapeutic targets. Mutations in the TTI2 gene have been implicated in a rare and severe form of ID, often accompanied by additional clinical manifestations. Despite the severity of this pathology, research on this gene remains limited. This project aims to generate novel insights into the role of TTI2 in human neuronal function and to elucidate how their mutations contribute to ID. To achieve this, we will employ human-derived cortical glutamatergic neurons as a model system, leveraging state-of-the-art methodologies to uncover potential therapeutic targets.