Our Mission:
The Luka Shai Foundation exists to accelerate treatments for ATP6AP2 and V-ATPase–related disorders and to support families facing ultra-rare, proton pump–related diseases. We believe every child deserves access to early diagnosis, informed care, and targeted therapeutics — and we work every day to make that future a reality.
Why We Exist
When our son Luka was diagnosed with an ATP6AP2-related condition — one of the rarest and least understood disorders in the world — we discovered first-hand how isolating, fragmented, and unsupported rare-disease families can feel. Answers were limited. Resources were scarce. Treatments didn’t exist.
We founded this organization so no family would have to navigate that journey alone.
Our Approach:
We combine lived experience with scientific rigor to push research forward and build the global collaborations this disease urgently requires.
We focus on four core pillars:
1. Advancing Research
We fund high-impact projects in molecular biology, glycosylation, proteomics, V-ATPase biology, and microbiome science. We support mouse-model development, cell-line generation, and translational pathways that move discoveries toward therapeutic options.
2. Building a Global Scientific Network
We partner with leading clinicians, researchers, and institutions across CDG, genetics, hepatology, neurology, and metabolism. Collaboration accelerates discovery, and we connect experts who might otherwise never cross paths.
3. Supporting Families & Clinicians
We provide clear, accessible information about ATP6AP2-related disease, early signs, genetic testing, and clinical management. Our patient registry and natural history study help families contribute directly to research progress.
4. Raising Awareness
We work to increase recognition of ATP6AP2-related disorders, improve diagnostic pathways, encourage early genotyping, and help the broader rare-disease community understand the role of proton pumps and glycosylation in human health.
How helping 1 patient can help 150,000 patients!!!
and it’s just the beginning…
Luka inherited an X-linked missense mutation that results in a loss-of-function defect in ATP6AP2, an essential assembly factor of the vacuolar H+-ATPase (V-ATPase) complex, also known as the proton pump. This complex plays a crucial role in regulating intracellular pH, enabling protein synthesis, degradation, and elimination across multiple biological pathways. While this mutation has been classified as a subset of Congenital Disorders of Glycosylation (CDG), it also falls within a broader category of V-ATPase-related defects, linking it to lysosomal storage disorders (LSDs) and neurological conditions.
When Luka was diagnosed in December 2021, we were stunned to learn that there were only four known patients in the world with this disease.
A few months later, in collaboration with GeneDx, we identified 15 additional potential ATP6AP2 patients, along with 19 ATP6AP1 patients—ATP6AP1 being a closely related “sister mutation.”
Suddenly, instead of just 1 patient, we had around 30 patients, but we knew this was just the beginning. There are other V-ATPase-related disorders involving assembly factors and subunits of the proton pump that could greatly benefit from being included in our research. These include ATP6AP1, ATP6V1A, ATP6V1G1, ATP6V0A2, and ATP6V0D1—bringing the estimated patient count to around 150 individuals.
To expand our reach, we can establish targeted patient acquisition channels by leveraging:
Phenotypic screening to identify undiagnosed cases
Search engine and social media data to enhance patient discovery
Outreach to specialists who frequently encounter these conditions and can refer potential patients to our study
But this goes even further. There are 16 subsets of CDGs that are impaired by acidification defects, including those affecting Golgi homeostasis. This expands our potential patient population to an estimated 70,000 individuals.
Identifying common phenotypic patterns across adjacent mutations would broaden our target disease population—not just for research but also for therapeutic development.
And defective proton pump function isn’t just linked to CDGs—it also drives Lysosomal Storage Disorders (LSDs). Both categories share a root cause: enzyme dysfunction and/or acidification defects. Now, we're talking about a patient population of at least 150,000 individuals.
By redefining subsets of LSDs and CDGs based on overlapping deficiencies, we can pinpoint “enzyme deficiencies” driven by acidification defects—allowing us to develop a truly targeted therapeutic approach for these conditions.
Let’s Aim Higher:
We’re not stopping at CDG. Because the V-ATPase proton pump is essential in so many basic processes — from cell pH regulation to autophagy, from brain development to metabolic health — the implications of our research could go far beyond any single disorder.
With your support, we believe we can unlock breakthroughs that impact:
Neurodevelopment & aging (brain health across the lifespan)
Cellular pH and organ function: kidneys, liver, heart, brain
Metabolism and metabolic disease pathways
Immune regulation, autophagy, inflammation
We’re building more than a foundation — we’re building a scientific movement. Let’s widen the circle, deepen the research, and offer hope to hundreds of thousands of families who have been invisible for too long.
Our Values:
Our Values
Compassion
Families are at the center of everything we do — their stories, challenges, and hopes guide our work.
Rigor
We invest only in research grounded in excellence, transparency, and scientific integrity.
Urgency
Rare disease cannot wait. We move with intention, efficiency, and purpose.
Collaboration
Progress happens when science, medicine, families, and advocacy come together.
Impact
Every project, partnership, and dollar raised must meaningfully move the field forward.
Our Vision:
A world where children with ATP6AP2-related and V-ATPase-related disorders receive early, accurate diagnoses — and where targeted, effective treatments are available within their lifetimes.
Our Commitment:
We are here for the children, the families, the researchers, and the clinicians — and for every person working to understand and treat ATP6AP2-related disorders. Together, we can bring clarity, connection, and hope to a disease that has lived in the shadows for too long.