Learn more about this rare disease, how it affects our families, and how we're helping to find treatment.
2026 Research Priorities
DLG4 is a gene that is critical for proper brain development. When it is disrupted, children with DLG4 SHINE Syndrome face severe neurological challenges, including Epilepsy, Intellectual disability, Autism, Speech delay or lack of speech, Low muscle tone, and Sleep disorders.
Without targeted treatment, these children require lifelong, round-the-clock care. Every project below is aimed at the root cause of the disorder, with the goal of improving quality of life for these children today and in the future.
In 2026, the Foundation is focused on six priorities. Together they cover three promising therapeutic strategies, the patient-derived tools researchers need, and the community that makes this work possible.
Giving Tuesday, December 1, 2026: Thanks to some extremely generous donor pledges, all donations up to $200,000 will be matched. This means that each dollar you donate is doubled!
Goal: $140,000 | Lead: Dr. Rami Aqeilan, Hebrew University of Jerusalem
Where we are. After four years of research, we are getting closer to determining which DLG4 gene therapy is ready to move toward clinical development. Dr. Aqeilan and his team have already shown that our AAV9 DLG4 gene therapy can restore PSD-95 in DLG4 patient-derived neurons and improve important cellular and synaptic measures.
The next challenge. Before moving into expensive manufacturing and clinical testing, we need to make sure we choose the safest and most effective version of the therapy.
What this funding does. This 18-month study will compare two versions of the gene therapy, with and without a component called WPRE. The comparison will be run directly in three existing DLG4 patient-derived cell lines and in mice. The goal is to determine which version provides the best balance of restoring PSD-95 while avoiding excessive expression or abnormal brain activity. We will also scientific consult with advisors who will guide us through all the steps we need to take towards clinical preparedness.
Why it matters. This study is an important step toward locking in the gene therapy design that can move into manufacturing and future clinical trials.Goal: $35,000 | Lead: Dr. Kim Dore, Assistant Professor of Neurosciences, UC San Diego
The science behind it. Dr. Dore has spent years studying PSD-95, synaptic function, and a process called palmitoylation in Alzheimer's disease. Her research has shown that palmitoylation helps keep PSD-95 at the synapse, where it is needed for normal communication between brain cells. Her team has demonstrated in Alzheimer's disease models that increasing PSD-95 palmitoylation can improve synaptic function and memory.
Latest results. Her research, published in 2026 in Communications Biology, showed that blocking the enzymes that remove palmitoylation from PSD-95 restored PSD-95 palmitoylation and rescued memory and synaptic deficits in female Alzheimer's mice.
The question for DLG4. Dr. Dore now wants to determine whether the same strategy could benefit children with DLG4 SHINE disorder by increasing the amount of functional PSD-95 at the synapse, without simply overexpressing the protein.
What this funding does. The first step is to test two depalmitoylation inhibitors, Palm B and ABD957, in approximately 6 to 10 DLG4 patient-derived iPSC lines representing different mutations and both sexes. The team will then measure whether these treatments increase PSD-95 palmitoylation and restore PSD-95 levels in the patient-derived neurons. If these six-month experiments are successful, the next step will be testing the approach in mice.
Budget. The pilot study will cost $35,000 for reagents and technician support.Goal: $75,000 | Lead: Dr. Jeff Coller, Johns Hopkins University
The approach. Last year, we began funding Dr. Coller's team to explore a novel therapeutic strategy that works by increasing the amount of protein produced from the patient's existing DLG4 gene. Rather than replacing the gene, this approach uses an engineered RNA "booster" designed to bind to DLG4 mRNA and extend its lifespan, giving the cell more time to translate that message into PSD-95 protein.
Progress so far. Johns Hopkins has already demonstrated that this technology can increase protein production in laboratory models. Early testing for DLG4 has produced encouraging results.
What this funding does. The next step is to optimize the approach specifically for DLG4. Continued funding will allow Dr. Coller's team to evaluate the most promising sequences in DLG4-relevant cell lines and determine whether this strategy can meaningfully increase DLG4 expression and PSD-95 production.
Why it matters. If successful, this could provide a mutation-independent therapeutic approach that works with the patient's own cellular machinery rather than requiring replacement of the DLG4 gene.Goal: $100,000 | Scientific and Family Conference 2027, July 2027
Our annual Scientific and Family conference brings families, doctors, researchers, and experts together in one place. Families can learn about the latest research, connect with other families who understand their journey, and speak directly with the scientists working toward treatments.
Why a family conference matters in a rare disease
When a condition is this rare, families can feel very alone. A family may never meet another who understands their child's daily reality, and the doctors near them may never have treated another patient with the same diagnosis. The conference gives families a place where no one has to explain.
For families, the conference means:
Community. Parents and siblings meet others who truly understand, share what has worked, and leave knowing they are not alone.
Answers in plain language. Families hear about the latest research and ask the scientists and clinicians working on DLG4 SHINE their questions directly.A voice in the research. In rare disease, families are partners in the science. Researchers who meet the children behind the data are more motivated, and more likely to stay with our disorder.
A way to contribute. With phlebotomists onsite, families can donate blood to the biorepository (see Priority 5), giving researchers the patient samples they need.For scientists, the conference builds the relationships that bring new labs and collaborations to DLG4 SHINE Syndrome, and it keeps the urgency of families' needs in front of the people who can help.
Your support will help us bring this community together in July 2027 and make sure families have access to the information and support they need.
Can't donate? Ask a local business to sponsor
A gift isn't the only way to help. If donating isn't possible for you right now, you can still make a real difference by reaching out to businesses in your community about sponsoring the Family Conference. Sponsorship helps keep the event accessible to families and brings new supporters into our community.
Here is how to get started:
Think of businesses that already know you. Your employer, the places your family shops, local restaurants, medical and therapy practices, banks, and community or civic groups are good first conversations.
Ask about corporate giving and employer matching. Many companies have community-giving budgets or match employee contributions, and a personal request from an employee or customer goes a long way.
Consider in-kind support too. Businesses may be able to help with things the conference needs, such as meals, printing, supplies, or event services, in place of or in addition to a cash gift.
Share your story. Tell them about your child, why the conference matters to your family, and what a rare disease community means to you.
Connect them with us. Reach out to the Foundation through dlg4shine.org and we will follow up with the business directly.Goal: $25,000
We have already built a world-class DLG4 SHINE Syndrome biorepository with more than 75 plasma and PBMC samples, creating a valuable resource that is helping attract researchers to our disorder. We need to keep that momentum going.
At our family conference, professional phlebotomists will be onsite so families can safely donate blood. This allows us to expand our collection and give researchers access to the patient samples they need to better understand SHINE Syndrome and accelerate the development of treatments.Goal: $25,000 | Partner: Cincinnati Children's Hospital
Researchers at Cincinnati Children's Hospital are creating two mouse models carrying DLG4 variants found in children with SHINE Syndrome. These patient-derived models will allow researchers to study how specific DLG4 variants affect brain function, including seizures, motor skills, learning and memory, sleep, and social behavior.
This work will give us a deeper understanding of how SHINE Syndrome affects the brain and provide critical data to guide future treatment development. Your donation will help fund the behavioral and neurological testing needed to turn these patient-specific models into valuable research tools for the SHINE community.
Plain-language Glossary
This glossary of terms was put together to help provide an understanding about the research projects mentioned above.
Plasma and PBMC samples:
Blood components stored in our biorepository for researchers to study.
mRNA:
The message copied from a gene that the cell reads to build a protein.
Palmitoylation:
A chemical tag that helps keep PSD-95 anchored at the synapse.
Patient-derived neurons / iPSC lines:
Brain cells grown in the lab from cells donated by people with DLG4 variants, so researchers can test therapies on real patient genetics.
WPRE:
A component that can be included in a gene therapy design. Researchers are testing versions with and without it to find the safest, most effective balance.
AAV9 gene therapy:
A therapy that uses a harmless viral carrier (AAV9) to deliver a working copy of a gene into cells.
PSD-95:
A protein made from the DLG4 gene. It sits at the synapse, the connection point between brain cells, and is needed for normal communication between them.
How You Can Help
Spread Awareness
Use the hashtags #DLG4SHINE, #DLG4SHINEGT2026, and #GivingTuesday to share our mission.
Fundraise
Start a personal fundraiser and share your story on social media. Text DLG4SHINE to 44-321 to direct friends and family to our donation page.
By Check
Make it payable to DLG4 SHINE Foundation and mail to:
DLG4 SHINE Foundation
c/o PSM Registered Agent LLC
2775 Orchard Run Road
Dayton, OH 45449
Donor Advised Funds
Donations through Donor Advised Funds can be directed to the DLG4 SHINE Foundation using our Tax EIN #87-4703593. This number can be used on any giving platform to send funds directly to us. For faster processing, please send any check to our PO Box address.
Donate
Every dollar counts! Giving Tuesday is on December 1st 2026. In the spirit of generosity this time of year brings, our Giving Tuesday Fundraising campaign will run from November 1st to December 31st and every donation will be matched 1:1 up to $200,000.