VWA8 is a mitochondrial matrix-targeted protein with ATPase activity that plays critical roles in cellular energy metabolism and mitochondrial homeostasis. 1 The protein contains a von Willebrand factor A domain and Walker A/B motifs essential for ATP hydrolysis activity. 1 VWA8 exists as two splice variants (VWA8a and VWA8b) with tissue-dependent expression patterns, particularly enriched in metabolically active tissues including liver, kidney, heart, and skeletal muscle. 12 Mechanistically, VWA8 exhibits structural homology to dynein motor proteins and functions in mitochondrial-dependent cellular processes. 12 VWA8 defects impair mitochondrial function, triggering excessive mitophagy and apoptosis activation. 3 Clinically, VWA8 mutations cause autosomal-dominant retinitis pigmentosa (RP), a progressive retinal dystrophy. 3 Zebrafish models with VWA8 knockdown recapitulate clinical RP phenotypes, confirming its role in retinal development and visual function. 3 Beyond RP, reduced VWA8 expression associates with increased risk for multiple sclerosis and sepsis, while genetic polymorphisms correlate with immune checkpoint inhibitor-related adverse events. 456 VWA8 emerges as a diagnostic biomarker in heart failure with preserved ejection fraction. 7