DMXL1 (Dmx-like 1) encodes a large WD repeat protein that serves as a critical regulator of lysosomal acidification and V-ATPase assembly 1. The protein is highly evolutionarily conserved across species, suggesting an important cellular function 1. DMXL1 functions as part of the metazoan RAVE (mRAVE) complex, assembling with ROGDI and WDR7 to facilitate V-ATPase assembly on lysosomal membranes 23. Upon TRPML1 activation, DMXL1 is recruited to lysosomes in a CASM-dependent manner and promotes V1 subunit recruitment, maintaining proper lysosomal pH and hydrolytic capacity 3. The protein also regulates phagosome acidification through TPL-2 kinase-mediated phosphorylation, which is essential for bacterial killing in macrophages 4. Loss of Dmxl1 in mice causes early embryonic lethality, confirming its essential role in basic cellular functions 5. Clinically, DMXL1 is targeted for degradation by human cytomegalovirus to disrupt autophagy and lysosomal function 6, and variants in DMXL1 have been identified as candidate disease-causing mutations in Saudi Arabian patients 7. The protein's critical role in V-ATPase assembly makes it essential for multiple cellular processes including neurotransmitter loading and autophagy regulation 2.