Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum. Associates with the V0 complex of the vacuolar ATPase (V-ATPase) (PubMed:29127204). Interacts with ATP6AP2 (PubMed:29127204). The disease is caused by variants affecting the gene represented in this entry. VMA21 deficiency results in an increase of lysosomal pH from 4.7 to 5.2, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which up-regulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell. Belongs to the VMA21 family. Protein characterization data are from PubMed:19379691. Due to a number of errors in the figure panels, the article has been retracted but the authors stand by the validity of the main results and conclusions (PubMed:20873370).