# Control of Seizure and Migraine Susceptibility by GPR37L1

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $501,694

## Abstract

Project Summary
 Epilepsy and migraine have long been recognized as being linked in certain families, but the genetic basis
of this comorbidity in not well understood. We and others have recently found evidence in human genetic
studies that variation in GPR37L1 is a major contributor to epilepsy and migraine risk, especially in cases
where epilepsy and migraine are comorbid. GPR37L1 is expressed predominantly in astrocytes, and thus
studies on this receptor may lead to more general insights into how astrocyte dysfunction contributes to
epilepsy and migraine. The goal of this project is to elucidate the cellular and mechanistic basis by which
GPR37L1 regulates seizure and migraine susceptibility. We will assess the trafficking and signaling properties
of disease-associated GPR37L1 variants in astrocytes and also address the mystery of why GPR37L1
signaling appears to be dependent on the astrocytic context. Furthermore, we will study the seizure
vulnerability of knock-in mice harboring pathogenic human variants and also explore how astrocyte
development in human cortical organoids is affected by pathogenic variants of GPR37L1. Additionally, we will
assess mice lacking Gpr37L1 or expressing pathogenic Gpr37L1 variants for migraine-relevant phenotypes
and evaluate these mutant mice for changes in cortical circuit excitability that might inform both the migraine
and seizure phenotypes. These studies will provide novel insights into the fundamental biology of GPR37L1
and also pave the way for the development of novel GPR37L1-targeted therapeutics for the treatment of
epilepsy, migraine and other diseases.

## Key facts

- **NIH application ID:** 10279634
- **Project number:** 1R01NS123447-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Randy A. Hall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $501,694
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279634

## Citation

> US National Institutes of Health, RePORTER application 10279634, Control of Seizure and Migraine Susceptibility by GPR37L1 (1R01NS123447-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10279634. Licensed CC0.

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