Members of the SLC26 family of anion exchangers display a transport activity towards monovalent and/or divalent anions including sulfate, chloride, bicarbonate, iodide and oxalate. In humans, genetic abnormalities of SLC26A2, A3, A4, and A5, have been causally associated with several diseases (1). Interestingly in various epithelia, SLC26 members (SLC26A3, A4, A5, A6 and A9) form a complex with the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), the chloride/bicarbonate channel mutated in cystic fibrosis, and are able to regulate CFTR transport activity (2). We previously described SLC26A8, also known as Testis Anion Transporter 1 (TAT1), as a sperm-specific member of the SLC26 family (3). 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. By generating a knock out mouse model of Slc26A8 we demonstrated that Slc26a8 is required for sperm motility, sperm capacitation and male fertility (4). Recently we confirmed the essential role of SLC26A8 in human too by identifying mutations in SLC26A8, which impair the stability of the SLC26-CFTR complex in men presenting with male infertility due to impaired sperm motility (i.e. asthenozoospermia) (5). Although the functional cooperation of SLC26A8 with CFTR is now well established, the intrinsic activity of SLC26A8 remains poorly defined. In particular the anion selectivity of SLC26A8 together with its mode of transport and the upstream regulatory signalling pathways are not defined. In order to better characterize SLC26A8, we have set up a functional assay in Hela cells transiently transfected with SLC26 proteins and tested for their anion transport activity using N-(Ethoxycarbonylmethyl)-6-Methoxyquinolinium Bromide (MQAE), a chloride sensitive probe. Fluorescence emission associated with chloride effluxes was recorded upon shifting the extra-cellular medium composition from chloride/bicarbonate to gluconate/bicarbonate. The slopes of the curves associated with the fluorescence emission of SLC26A3 and A8 transfected cells were compared to that of cells transfected with an empty vector and not transfected cells. Our preliminary results indicate that unexpectedly, in contrast to the SLC26A3 protein, SLC26A8 does not behave as a chloride-bicarbonate exchanger (n=8. Student test: p=0,042).