SLC9C1 encodes a sperm-specific sodium/proton exchanger (sNHE) essential for male fertility and sperm motility 1. This plasma membrane transporter regulates intracellular pH homeostasis in spermatozoa and possesses a unique voltage-sensing domain 2. SLC9C1 functionally associates with soluble adenylyl cyclase (sAC) to regulate bicarbonate-dependent cAMP signaling pathways critical for sperm hyperactivation and capacitation 23. Unlike its sea urchin homologue, human SLC9C1 is not gated by voltage or cAMP but contributes to setting resting intracellular pH through amiloride-sensitive sodium/proton exchange 3. Mutations in SLC9C1 cause asthenozoospermia—reduced sperm motility without major flagellar morphological defects—establishing it as a novel genetic cause of human male infertility 14. The gene is differentially expressed in developing spermatids and its expression is regulated by DNA methylation-sensitive promoter elements conserved across mammalian species 56. Notably, SLC9C1 variants may also modify age of onset in Alzheimer's disease, suggesting broader physiological roles beyond reproductive function 7.