SLC26A8 is a sperm-specific anion transporter that mediates exchange of sulfate and oxalate against chloride ions across membranes. The protein physically associates with and strongly stimulates the anion transport activity of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, cooperating to regulate chloride and bicarbonate ion fluxes essential for sperm motility and capacitation. SLC26A8 localizes to the sperm annulus, a septin-based structure connecting the midpiece to the principal piece, and is critical for proper sperm tail differentiation 1. Pathogenic variants cause asthenozoospermia through multiple mechanisms. Heterozygous missense mutations impair SLC26A8 stability and abolish CFTR-dependent anion transport activation 2, while compound heterozygous mutations cause severe asthenozoospermia with midpiece defects including absence of the mitochondrial sheath and annulus 3. Complete loss of Slc26a8 in mice results in male sterility due to severely reduced sperm motility and abnormal flagellar differentiation 1. Recent evidence suggests SLC26A8 variants may also contribute to neurogenic inflammation in rosacea, with mutations inducing excessive vasoactive neuropeptide production in neural cells 4. SLC26A8 emerges as a druggable target for male contraception, with sperm-specific expression and essential roles in motility-dependent fertility 5. Understanding SLC26A8 function may enable development of reversible male contraceptives or therapies for infertility-associated variants.