SLC9A8 encodes NHE8, a Na+/H+ antiporter mediating electroneutral exchange of intracellular H+ for extracellular Na+ in 1:1 stoichiometry 1. Primary functions include regulating intracellular pH and Golgi apparatus pH, thereby controlling protein trafficking and endosomal morphology 23. In the intestinal epithelium, SLC9A8 plays a major physiological role in transepithelial Na+ absorption and maintains mucosal integrity 4. In retinal pigment epithelium, it regulates endosomal volume and pH essential for photoreceptor support 5. SLC9A8 dysfunction contributes to multiple diseases. Vitamin D/VDR-mediated upregulation of NHE8 protects against ulcerative colitis; compromised NHE8 expression exacerbates colitis through TNF-α/NF-κB pathway activation 6. In colorectal cancer, SLC9A8 downregulation promotes epithelial-mesenchymal transition and metastasis via IL6-JAK1/STAT3 signaling, with reduced expression associated with poor prognosis 7. SLC9A8 variants influence intestinal microbiota composition 8 and have been associated with inflammatory bowel disease susceptibility as part of a diagnostic blood transcriptomic panel achieving 99% accuracy 9. Recently, SLC9A8 variants were identified in frontotemporal dementia and amyotrophic lateral sclerosis genetic associations 10. Dietary factors including myricetin positively correlate with SLC9A8 expression 11.