Ion fluxes play an essential role in the control of sperm motility and capacitation (a maturation event occurring in the female genital tract and required for fertilization); in particular, calcium, chloride and bicarbonate are essential for both processes by activating cAMP-PKA-dependent phosphorylation pathways (1). We previously described SLC26A8, also known as Testis Anion Transporter 1 (SLC26A8), as a male germ cell-specific member of a large family of anion transporters (or sulfate permeases) known as SLC26 (Solute Linked Carrier 26) proteins (2). Most SLC26 proteins display transport activity towards monovalent and/or divalent anions (including sulfate, chloride, bicarbonate, iodide, oxalate) and in humans, genetic abnormalities of SLC26A2, SLC26A3, SLC26A4, and SLC26A, have been causally associated with diastrophic dysplasia, chloride diarrhea, Pendred syndrome and deafness respectively (3). We have previously shown that homozygous deletion of Slc26A8 in the mouse leads to male sterility due to the total lack of sperm motility, impairment of sperm capacitation and severe structural defects of the flagellum (midpiece disorganization, hairpin-like bending of the flagellum and atrophy of the annulus). (4). Consistent with this phenotype, SLC26A8 in mature sperm localizes at the equatorial segment of the head and at the annulus, a ring shape structure at the junction between the midpiece and the principal piece of the flagellum (4). In various epithelia, members of the SLC26 family (SLC26A3, A4, A5, A6 and A9) complex with the Cystic Fibrosis Transmembrane conductance Regulator, the chloride/bicarbonate channel mutated in cystic fibrosis, and are able to regulate CFTR transport activity (5). Interestingly, the CFTR channel has been shown to localize at the equatorial segment of the head and at the flagellum (midpiece) of mature sperm, and to be required for sperm motility and capacitation (6,7). We will report our recent findings about SLC26A8 and CFTR functional cooperation and the consequences of SLC26A8 mutations in human male fertility.