EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects
Saikat Ghosh1, Jaskaran Singh2, Nadirah S Damseh3
1Division of Neuroscience and Cellular Structure, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Brain : a Journal of Neurology
|October 8, 2025
Summary
Genetic variants in EIPR1 (EARP-interacting protein 1) cause a novel neurodevelopmental disorder by impairing endosomal recycling and vesicle biogenesis. This research identifies EIPR1 as crucial for nervous system development and function.
Area of Science:
- Cell Biology
- Genetics
- Neuroscience
Background:
- EIPR1 (EARP-interacting protein 1) is involved in protein transport via endosomes.
- Its role in human neurological disorders was previously unknown.
Purpose of the Study:
- To investigate the physiological and pathological importance of EIPR1 in humans.
- To identify the genetic basis of a novel neurodevelopmental disorder.
Main Methods:
- Identified EIPR1 variants in affected individuals.
- Performed cellular studies on variant effects on EIPR1 function.
- Utilized zebrafish models to confirm pathogenicity.
Main Results:
- Five EIPR1 missense variants were identified in six families with a neurodevelopmental disorder.
- Variants reduced EIPR1 levels, interaction with EARP/GARP complexes, and vesicle biogenesis.
- Zebrafish models recapitulated human phenotypes and showed rescue with wild-type EIPR1.
Conclusions:
- EIPR1 is a novel genetic locus for neurodevelopmental disorders.
- EIPR1 is critical for endosomal recycling and dense core vesicle biogenesis in the nervous system.
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