ATP2B2 encodes PMCA2, a plasma membrane Ca²⁺-ATPase that maintains basal intracellular calcium levels in specialized neurons and sensory cells 12. This ATP-driven pump transports cytosolic Ca²⁺ across the plasma membrane with rapid activation kinetics suited for controlling fast neuronal Ca²⁺ dynamics 12. In cerebellar circuits, PMCA2 mediates presynaptic Ca²⁺ efflux at parallel fiber-Purkinje neuron synapses, enabling fast Ca²⁺ return to resting levels and contributing to long-term depression and motor learning 12. In cochlear hair cells, it dissipates Ca²⁺ transients from mechanoelectrical transduction channels and regulates vestibular Ca²⁺ for otoconia formation, playing essential roles in hearing and balance 12. Clinically, heterozygous ATP2B2 variants cause autosomal dominant nonsyndromic hearing loss (DFNA82) 3. Beyond auditory deficits, de novo and inherited ATP2B2 variants cause variable neurodevelopmental disorders featuring ataxia, dystonia, intellectual disability, autism, and seizures, with cerebellar atrophy observed in some cases 34. Cell-based studies show variants produce altered cytosolic calcium handling with both loss- and gain-of-function effects 3. These findings highlight PMCA2's critical role in cerebellar development and precise calcium regulation for neurotypical development 4. GWAS analysis identified ATP2B2 as a common variant locus associated with autism spectrum disorder 5, and CRISPR-Cas9 gene editing targeting Atp2b2 mutations restored hearing in dominant hearing loss mouse models 6.