ATP8A2 is a P4-ATPase flippase that catalyzes ATP-dependent transport of aminophospholipids, particularly phosphatidylserine (PS) and phosphatidylethanolamine (PE), from the outer to inner leaflet of cell membranes 1. As the catalytic component of the ATP8A2:TMEM30A complex, it maintains asymmetric phospholipid distribution essential for neuronal and sensory function 2. ATP8A2 is required for normal visual and auditory function, supporting photoreceptor disk membrane organization and inner ear spiral ganglion cell survival, with proposed roles in neurite outgrowth and vesicle trafficking 3. Biallelic ATP8A2 mutations cause cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 (CAMRQ4), an autosomal recessive neurodevelopmental disorder 4. Clinical manifestations include severe psychomotor impairment, intellectual disability, hypotonia or spasticity, cerebellar atrophy, chorea, optic atrophy, and dental abnormalities 56. Disease-causing variants include missense mutations in catalytic domains (G447R, A772P) causing protein misfolding and degradation, and splicing variants disrupting proper mRNA processing 27. Recent evidence demonstrates ATP8A2 dysfunction leads to PS externalization and immune-mediated neurodegeneration, implicating neuroinflammatory mechanisms in CAMRQ4 pathogenesis and potentially ALS-FTD 3.