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Human OCTN (hOCTN) transporters are localized to the plasma membrane of the cell and are involved in the bidirectional transport of cations and zwitterions. The genes encoding hOCTN1 and hOCTN2 are found in relative proximity at the same locus on chromosome 5q31 [2]. Each are encoded by 10 exons, with hOCTN1 composed of 551 amino acids and hOCTN2 composed of 557 amino acids. They are homologues—with 78% sequence identity at the mRNA level and 76% sequence identity at the protein level. Additionally, these transporters share about 30% protein identity to the OCTs (OCT1–3). Similar to OCTs, OCTNs have predicted topology with 12 transmembrane domains, cytoplasmic N‐ and C‐termini, a large extracellular loop between TMD1 and TMD2 containing multiple glycosylation sites, and an intracellular nucleotide binding sequence motif [2]. Facilitating sodium‐dependent transport of some substrates, the OCTN transporters also contain sodium‐recognition sites and can function as symporters (Fig. 2.2b).

SLC22A15 and CT2 are both found on the plasma membrane and exhibit bidirectional function similar to OCTN1 and OCTN2. The genes encoding these transporters are found on distinct chromosomes, with SLC22A15 at locus 1q13 and SLC22A16 at locus 6q21. SLC22A15 contains 11 exons while SLC22A16 has two isoforms, one with 8 exons and one with 10 exons [76, 77]. SLC22A15 contains 547 amino acids, while CT2 contains 577 amino acids. SLC22A15 and CT2 have mRNA and protein sequence identity of 47% and 31%, respectively. While still considered family members of the OCTN subclade, these two transporters appear to have evolutionally diverged from each other and from the other two OCTNs [78]. SLC22A15 and CT2 have 50–52% mRNA sequence identity and 32–33% protein sequence identity to OCTN1 and OCTN2. However, the predicted topology of SLC22A15 and CT2 remains similar to OCTN1 and OCTN2, with 12 predicted transmembrane domains and cytoplasmic N‐ and C‐termini [1].