SLC9A1 encodes sodium/hydrogen exchanger 1 (NHE1), an electroneutral antiporter that extrudes intracellular protons in exchange for extracellular sodium, protecting cells from acidification. The transporter maintains intracellular pH and cell volume, critical for cell growth, proliferation, migration, and survival. SLC9A1 also anchors signaling scaffolds that coordinate cellular inputs. In cancer, elevated SLC9A1 expression correlates with tumorigenesis and poor prognosis. In gliomas, SLC9A1 mRNA levels are significantly higher in higher-grade tumors and associated with worse survival 1. The NHE1 inhibitor HOE642 reduced glioma volume and invasion while sensitizing tumors to anti-PD-1 therapy 1. In acute myeloid leukemia, downregulation of SLC9A1 through miRNA targeting increases sensitivity to cytarabine chemotherapy 2. In cardiovascular disease, NHE1 hyperactivity drives pathological hypertrophy and heart failure. The SGLT2 inhibitor empagliflozin protects against heart failure through NHE1 inhibition, independent of SGLT2 3. Cariporide, a selective NHE1 inhibitor, mimicked empagliflozin's cardioprotective effects 3. In heart failure with preserved ejection fraction patients, empagliflozin reduced sodium influx in atrial cardiomyocytes, suggesting anti-arrhythmic benefits 4. Germline SLC9A1 mutations cause neurological and reproductive phenotypes. Stop codon mutations at positions 321, 449, and 735 abolish transporter function through impaired plasma membrane targeting and protein stability 5.