Based on limited published evidence, VMA22 is an accessory component of the vacuolar proton-transporting V-ATPase complex essential for intracellular iron homeostasis. VMA22 enables endolysosomal acidification and lysosomal protein degradation 1. In aerobic conditions, VMA22 maintains iron levels necessary for Fe(2+) prolyl hydroxylase (PHD) enzyme activity, enabling HIF1A hydroxylation and proteasomal degradation 1. VMA22 may additionally participate in Golgi homeostasis. Mutations cause congenital disorder of glycosylation 2O, suggesting broader roles in protein processing and cellular homeostasis.