SLC8A1 encodes a sodium-calcium exchanger that mediates the bidirectional transport of one calcium ion against three to four sodium ions across the cell membrane, thereby regulating cytoplasmic calcium levels and calcium-dependent cellular processes. The exchanger plays a critical role in excitation-contraction coupling in cardiac muscle: following rapid calcium release from the endoplasmic reticulum through voltage-gated channels, SLC8A1 exports calcium from the cell to restore baseline cytoplasmic levels. The gene is required for normal embryonic heart development and the onset of heart contractions. SLC8A1 is subject to post-translational modification by palmitoylation, which affects its membrane localization and function. Recent evidence suggests that circular RNA derived from SLC8A1 (circSLC8a1) encodes a novel protein isoform (SLC8a1-604) that translocates to mitochondria and impairs ATP synthesis, contributing to cardiac remodeling under pressure overload 1. Additionally, SLC8A1 has been implicated in alternative splicing regulation by the cardiac RNA-binding protein RBPMS2, with disruption of this splicing affecting calcium handling and myofibrillar organization 2. Clinically, rare coding variants in SLC8A1 associate with cognitive function in the adult population 3. In cancer contexts, SLC8A1 inhibition with selective pharmacological agents such as CB-DMB significantly reduces proliferation and induces calcium-dependent cell death in gastric cancer cells, both alone and synergistically with cisplatin 4. In uveal melanoma with LKB1 loss, SLC8A1 upregulation drives tumorigenesis through increased intracellular calcium and mitochondrial reactive oxygen species; combination therapy targeting SLC8A1 and oxidative stress shows enhanced efficacy in these tumors 5.