SLC8A1 encodes the sodium-calcium exchanger NCX1, a plasma membrane antiporter that mediates the electrogenic exchange of one Ca²⁺ ion for three to four Na⁺ ions 123. This exchange is critical for cytoplasmic Ca²⁺ homeostasis and excitation-contraction coupling in cardiac muscle, where SLC8A1 exports intracellular Ca²⁺ during the repolarization phase following initial voltage-gated channel-mediated Ca²⁺ influx 123. SLC8A1 is subject to post-translational modification through palmitoylation, which modulates its membrane localization and function 4. Clinically, SLC8A1 dysfunction is implicated in cardiac arrhythmogenesis; genome editing to abolish SLC8A1 expression in human pluripotent stem cell-derived cardiomyocytes eliminates automaticity and prevents engraftment arrhythmias in transplantation models 5. Additionally, SLC8A1 regulation by the LKB1-SIK2 axis influences uveal melanoma progression through intracellular calcium and mitochondrial ROS accumulation, with SLC8A1 inhibition showing therapeutic potential 6. A circRNA-derived SLC8A1 protein isoform (SLC8a1-604) translocates to mitochondria and impairs cardiac function by suppressing mitochondrial gene transcription 7. SLC8A1 variants are also associated with cognitive function in adults 8, and alternative splicing of SLC8A1 requires the myocardial regulator RBPMS2 9.