International V-ATPase Awareness Day Date in the current year: July 23, 2026

V-ATPase (short for vacuolar-type ATPase) is an enzyme with a diverse range of functions. It acts as a proton pump, using energy from ATP (adenosine triphosphate, the cell’s main immediate energy carrier) to transport hydrogen ions across cellular membranes. This process creates an acidic environment in various cellular compartments, such as lysosomes, which is essential for many cellular processes, including breaking down damaged cell components, recycling cellular materials, and supporting the transport of certain molecules.

V-ATPase is not a single protein, but rather a protein complex made up of multiple subunits, each with a specific biological role. Many of its subunits are encoded by more than one gene. A total of 23 genes encode the various subunits that make up V-ATPase; a mutation in even one of these genes can lead to severe, multisystem genetic disorders. However, there are also tissue-specific V-ATPase-related disorders.

Many V-ATPase-related disorders affect the brain, resulting in neurological symptoms such as developmental delay, intellectual disability, and seizures. They may also impact the muscles (low muscle tone and movement disorders), bones (abnormally dense yet fragile bones), kidneys (kidney stones and metabolic acidosis), the inner ear (sensorineural hearing loss), and connective tissues.

Some of the best-known V-ATPase-related conditions include osteopetrosis, distal renal tubular acidosis (dRTA), and X-linked myopathy with excessive autophagy (XMEA). Osteopetrosis, also known as marble bone disease, is characterized by abnormally dense and brittle bones. This is because osteoclasts, the cells responsible for bone remodeling, cannot reabsorb bone tissue properly.

Distal renal tubular acidosis (dRTA) primarily affects the kidneys. V-ATPase dysfunction prevents them from properly acidifying urine, which leads to metabolic acidosis (an abnormally acidic pH level in the body) and kidney stones. The same mutation may also cause sensorineural hearing loss.

X-linked myopathy with excessive autophagy (XMEA) primarily affects skeletal muscles, resulting in slowly progressive weakness that typically begins in the legs. Onset usually occurs in childhood, and some patients eventually become wheelchair-bound as they age.

Other V-ATPase-related disorders include developmental and epileptic encephalopathy, cutis laxa, skin and joint laxity, DDOD (dominant deafness-onychodystrophy) syndrome, Zimmerman-Laband syndrome, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures) syndrome, neurodevelopmental disorder with DOORS-like features, and short stature and osteoporosis.

All V-ATPase-related disorders are extremely rare, meaning they are difficult to diagnose and families affected by these disorders may lack access to treatment, resources, and support. International V-ATPase Awareness Day was created by the nonprofit organization V-ATPase Alliance to support individuals and families affected by V-ATPase deficiencies and advocate for further research into these disorders.