SLC8A3 (NCX3) encodes a sodium/calcium exchanger that mediates electrogenic Ca2+ export in exchange for Na+ influx across the cell membrane 1. This transporter is critical for maintaining intracellular calcium homeostasis in excitable tissues, particularly in brain and muscle, by rapidly restoring baseline Ca2+ levels following activation 2. SLC8A3 also functions in mitochondrial calcium homeostasis, regulating calcium efflux from mitochondria and supporting mitochondrial bioenergetics 3. The protein is essential for oligodendrocyte differentiation and myelination [UniProt reference via 45]. SLC8A3 exists as multiple tissue-specific isoforms produced through alternative splicing, with NCX3.2 predominant in brain and NCX3.3/3.4 variants in muscle 1. Disease relevance includes autism spectrum disorder, where SLC8A3 variants have been identified as potentially pathogenic candidates 5, and cancer, where SLC8A3 knockdown reduces cell proliferation and migration while promoting apoptosis in colorectal and lung squamous carcinoma cells 67. Additionally, SLC8A3 expression is regulated by TGF-β signaling to prevent oxidative stress in developing dopaminergic neurons 2, and altered SLC8A3 expression promotes atrial arrhythmogenesis 8.