Maedi Visna (MV) is a chronic lentiviral disease of sheep that causes severe debilitation and production losses worldwide. Clinical disease is commonly fatal, after a long asymptomatic but infectious period. There are no vaccines for MV and control options are restricted to husbandry practice changes and test and cull programmes, which may have limited effectiveness. Genetic selection for MV resistance has emerged as an attractive strategy for reducing losses to MV.  A change of amino acid 35 from glutamic acid (E) to lysine (K) in the TMEM154 protein has been associated with significant reduction in MV virus (MVV) infection and clinical disease in homozygous sheep. However, the cellular function of TMEM154 and its role, if any, in MV pathogenesis are unknown. This knowledge is required to underpin a breeding programme to select for resistant sheep. Our results show that TMEM154 is expressed on the plasma membrane of sheep cells, with an extracellular N-terminus containing amino acid 35E/K. Virus entry assays using MVV reporter viruses have identified enhanced infection in cells overexpressing either form of TMEM154, suggesting a role for TMEM154 in an early step of the MVV infection cycle. Work is ongoing to further characterise the role of TMEM154 in MVV entry. We are also seeking to identify TMEM154 binding partners, to understand the normal cellular function of this protein. Our findings begin to elucidate the structure, localization, and function of TMEM154 and will be combined with further work to determine its impact on both health and disease.