SLC8A2 encodes a sodium-calcium exchanger (NCX2) that mediates the electrogenic exchange of Ca²⁺ against Na⁺ ions across cell membranes, contributing to intracellular calcium homeostasis 1. The protein is specifically expressed in brain tissue and plays crucial roles in neuronal function and calcium regulation 2. SLC8A2 functions as a tumor suppressor gene in gliomas, where its expression is silenced through DNA methylation of gene-body CpG islands 2. Restoration of SLC8A2 expression inhibits glioblastoma invasion, migration, and angiogenesis by inactivating ERK1/2 signaling pathways and reducing matrix metalloproteinase levels 3. The gene contributes to cardiac calcium homeostasis, with deficiency promoting atrial arrhythmogenesis under adrenergic stress through enhanced RyR2 phosphorylation and altered calcium handling 1. SLC8A2 serves as a prognostic biomarker in colon adenocarcinoma, where high expression correlates with better patient outcomes 4. Loss of SLC8A2 function through 19q13.32 microdeletions contributes to a recognizable syndrome characterized by developmental delays, facial asymmetry, and multiple organ system abnormalities 5. The gene also shows potential as a biomarker for severe acute mountain sickness prediction 6.