Recent advances in the clinical spectrum and pathomechanisms associated with X-linked myopathy with excessive autophagy and other VMA21-related disorders

X-linked myopathy with excessive autophagy (XMEA) is a rare neuromuscular disorder caused by mutations in the VMA21 gene, encoding a chaperone protein present in the endoplasmic reticulum (ER). In yeast and human, VMA21 has been shown to chaperone the assembly of the vacuolar (v)-ATPase proton pump required for the acidification of lysosomes and other organelles. In line with this, VMA21 deficiency in XMEA impairs autophagic degradation steps, which would be key in XMEA pathogenesis.[…] In this review, we discuss recent advances on the clinical spectrum associated with VMA21 deficiency and on the pathophysiological roles of VMA21.