SLC9A1 encodes the sodium/hydrogen exchanger 1 (NHE1), an electroneutral antiporter that extrudes intracellular sodium in exchange for extracellular protons in 1:1 stoichiometry, protecting cells from acidification caused by metabolic activity 1. The transporter maintains intracellular pH neutrality and cell volume, functions essential for cell growth, proliferation, migration, and survival 2. SLC9A1 also transports lithium and functions as a Na+/Li+ antiporter 3, while serving as a membrane anchoring scaffold for signaling complexes 4. Structurally, NHE1 comprises a 500-amino acid membrane domain forming 12 transmembrane segments and a 315-amino acid cytosolic regulatory tail; early stop codon mutations cause rapid protein degradation and loss of plasma membrane targeting and activity 5. Point mutations disrupting the cation binding site abolish exchanger activity despite normal surface targeting 6. Diseased states include Lichtenstein-Knorr syndrome 7. SLC9A1 dysregulation occurs in acute myeloid leukemia, where miR-12462-mediated downregulation associates with increased chemotherapy sensitivity 8. In breast cancer, SLC9A1 upregulation promotes proliferation and migration through sodium homeostasis dysregulation and is an independent prognostic biomarker 9. Recent work demonstrates that empagliflozin's cardioprotective effects in heart failure operate through NHE1-NO pathway inhibition independent of SGLT2 10.