The Tdark TRAPPC8 and PCDH19: Exploring their interplay in intracellular trafficking as a new converging pathway between neurodevelopmental TRAPPopathies and PCDH19-related epilepsy syndrome

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

The project aims to study TRAPPC8, a gene located on chromosome 18 whose function is largely unknown. TRAPPC8 encodes a protein that is part of TRAPP complexes. These are multi-protein assemblies crucial for intracellular protein trafficking, allowing the movement of other proteins through cellular compartments to reach their final destination within the cell. Mutations in various subunits of TRAPP complexes lead to neurodevelopmental disorders collectively known as TRAPPopathies. Our preliminary data suggest an interplay between TRAPPC8 and PCDH19, a protein involved in delivering the neurotransmitter receptor GABA(A) to the cell surface. Importantly, PCDH19 gene mutations cause Developmental and Epileptic Encephalopathy 9 (DEE9), which shares clinical manifestations with TRAPPopathies. We therefore plan to investigate TRAPPC8-PCDH19 interplay in neurons to gain a better understanding of the pathogenic mechanisms underlying TRAPPopathies and DEE9.