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Gastric Proton Pumpopathy Associated with Protein Sorting Machinery: A Narrative Review
Aime Patrick Niyomugabo1, Leopold Ntakirutimana1, Jean Claude Habineza1
1Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda.
Clinical and Experimental Gastroenterology
|March 27, 2026
Summary
Defects in protein sorting disrupt the gastric proton pump, impairing acid secretion. Targeting these sorting mechanisms offers new therapies for gastric acid disorders, including PPI-resistant cases.
Area of Science:
- Cell biology
- Gastroenterology
- Molecular medicine
Background:
- Gastric acid secretion relies on H⁺/K⁺-ATPase-rich tubulovesicle (TV) trafficking to the apical membrane.
- The role of protein sorting machinery in gastric acid dysregulation is not well understood.
- This review examines protein sorting in gastric proton pumpopathy and acid secretion.
Purpose of the Study:
- To review the role of protein sorting machinery in gastric acid secretion.
- To understand the mechanisms of gastric proton pumpopathy.
- To identify potential therapeutic targets for gastric acid disorders.
Main Methods:
- Literature search of PubMed, Wiley, and African Journal Online.
- Inclusion of 15 original research articles published between 1988 and 2025.
- Synthesis of evidence on protein sorting machinery in gastric acid regulation.
Main Results:
- Misfolded proton pump subunits are degraded, impairing acid secretion.
- Defective vesicular transport (COP II/I) and Rab GTPase activity disrupt proton pump delivery.
- Dysregulated SNARE complexes and adaptor proteins impede vesicle fusion and endosomal recycling.
Conclusions:
- Defects in protein sorting machinery cause gastric proton pumpopathy and impaired acid secretion.
- Protein sorting regulators are potential therapeutic targets for restoring pump localization.
- Targeting upstream mechanisms may offer solutions for PPI-resistant and congenital gastric acid disorders.
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