DMXL2 is a scaffold protein that assembles the metazoan V-ATPase complex, functioning as part of the mRAVE (metazoan RAVE) complex alongside ROGDI and WDR7 1. Within this complex, DMXL2 interacts with V1 and VO subunits to facilitate their association upon proton gradient dissipation, enabling lysosomal acidification and synaptic vesicle function 1. In hair cells, DMXL2 is essential for synaptic vesicle endocytosis and recycling at ribbon synapses, maintaining the reserve pool of vesicles critical for sustained neurotransmission 2. Additionally, DMXL2 promotes V1-ATPase recruitment to lysosomes in response to TRPML1 activation, with DMXL2-deficient cells showing reduced V1 recruitment, increased lysosomal pH, and diminished hydrolytic capacity 3. In the hypothalamus, DMXL2 expression increases during postnatal development and pubertal transition, suggesting a role in neuroendocrine regulation of reproduction 4. Disease associations include autosomal dominant nonsyndromic sensorineural hearing loss (DFNA71) 25, developmental and epileptic encephalopathy 81, and neurodevelopmental disorders including autism spectrum disorder 6. Mutations cause impaired synaptic function and disrupted homeostatic processes, highlighting DMXL2's critical role in neuronal and endocrine function.