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While the export of substrates out of cells is mediated by ATP-binding cassette (ABC) transporters, SLC (solute carrier) transporters are mainly responsible for the uptake into cells. In contrast to most well-characterised ABC transporters, many SLC transporters have been studied insufficiently. Such transporters are called orphan transporters. Despite the fact that the\n                      <jats:italic>SLC21<\/jats:italic>\n                      \/\n                      <jats:italic>SLCO<\/jats:italic>\n                      family contains several important transporters for widely prescribed drugs, one of its family members, OATP5A1 (\n                      <jats:italic>SLCO5A1<\/jats:italic>\n                      ), is such an orphan transporter. OATP5A1 is ubiquitously expressed throughout the body, including expression in the brain, heart, intestine and various cancerous tissues. However, no substrates have been characterised for this transporter to date.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using stably-transfected HEK293 cells overexpressing human OATP5A1 (HEK-OATP5A1) and the respective control cells (HEK-VC), we investigated known substrates of other OATP family members as potential OATP5A1 substrates. Furthermore, an untargeted metabolomics analysis of both cell lines was performed after incubation with human plasma. Candidate substances were further characterised as substrates of OATP5A1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After characterisation of the stably-transfected HEK-OATP5A1 cells, uptake assays and untargeted metabolomics analysis identified the hormone conjugate estrone-3-sulfate, the amino acids glutamine, glycine and tyrosine, the vitamins pantothenic acid (vitamin B\n                      <jats:sub>5<\/jats:sub>\n                      ) and thiamine (vitamin B\n                      <jats:sub>1<\/jats:sub>\n                      ) and the nucleotide thymine as potential OATP5A1 substrates. While estrone-3-sulfate, tyrosine and thiamine were further characterised as uptake substrates, glutamine and glycine were exported by OATP5A1. Moreover, pantothenic acid and thymine inhibited OATP5A1-mediated tyrosine uptake. For estrone-3-sulfate, tyrosine and thiamine, kinetic transport parameters (K\n                      <jats:sub>m<\/jats:sub>\n                      values) of 102.2\u00a0\u00b5M, 169.9\u00a0\u00b5M and 15.6\u00a0\u00b5M were calculated, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the present study, OATP5A1 was deorphanised by characterising amino acids and vitamins as substrates of this transport protein. Estrone-3-sulfate, tyrosine and thiamine were taken up by OATP5A1. Moreover, OATP5A1 mediated the efflux of the amino acids glutamine and glycine, which play essential roles in brain function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s11658-026-00943-7","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:54:59Z","timestamp":1780422899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deorphanisation and functional characterisation of OATP5A1 as transport protein for amino acids and vitamins"],"prefix":"10.1186","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4376-4367","authenticated-orcid":false,"given":"Elena","family":"Kohlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0343-8569","authenticated-orcid":false,"given":"Nikola K.","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-4231","authenticated-orcid":false,"given":"Arne","family":"Gessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0334-7478","authenticated-orcid":false,"given":"Martin F.","family":"Fromm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-5482","authenticated-orcid":false,"given":"J\u00f6rg","family":"K\u00f6nig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"943_CR1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrd4626","volume":"14","author":"L Lin","year":"2015","unstructured":"Lin L, Yee SW, Kim RB, Giacomini KM. 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