Abstract

The solute carrier proteins (SLCs) comprise a superfamily of transporters controlling the import and export of molecules across membranes thus playing essential roles in a multitude of physiological and pharmacological processes. With more than 450 members, SLCs are the largest family of transporters encoded by the human genome. Genetic studies have evidenced- that a perturbation of SLC transporters’ function underlies numerous human common and rare diseases, thus making SLC transporters attractive drug targets. Despite this, SLCs have been long under-explored and indeed less than 5% of all the SLC transporters are currently targeted by approved drugs. The development of SLC functional assays for running high-throughput screening campaigns represents a fundamental approach to discover novel inhibitors and activators of SLC transporters for therapeutic purposes. Axxam has applied its consolidated experience and expertise in assay development for the generation of functional assays for many different SLCs, applying multiple and diversified technologies including but not limited to genetically encoded sensors -, fluorescent dyes and substrates -, optogenetic-, radiometric- and imaging- based detection methods. In this conference we would focus on SLCs case studies whose mutations and loss-of-function are crucial for rare diseases onset and progression. The first case study is SLC6A8 whose frameshift and splicing mutations induce X-linked creatine transporter deficiency, a rare X-linked single gene disorder. The second case study is SLC26A9 whose rare loss-of-function mutations are involved in Idiopathic diffuse Bronchiectasis, a chronic lung disease that resembles cystic fibrosis in many aspects.