The neutral amino acid transporter subfamily that consists of six members, consecutively SLC6A15–SLC620, also called orphan transporters, represents membrane, sodium-dependent symporter proteins that belong to the family of solute carrier 6 (SLC6). Primarily, they mediate the transport of neutral amino acids from the extracellular milieu toward cell or storage vesicles utilizing an electric membrane potential as the driving force. Orphan transporters are widely distributed throughout the body, covering many systems; for instance, the central nervous, renal, or intestinal system, supplying cells into molecules used in biochemical, signaling, and building pathways afterward. They are responsible for intestinal absorption and renal reabsorption of amino acids. In the central nervous system, orphan transporters constitute a significant medium for the provision of neurotransmitter precursors. Diseases related with aforementioned transporters highlight their significance; SLC6A19 mutations are associated with metabolic Hartnup disorder, whereas altered expression of SLC6A15 has been associated with a depression/stress-related disorders. Mutations of SLC6A18-SLCA20 cause iminoglycinuria and/or hyperglycinuria. SLC6A18-SLC6A20 to reach the cellular membrane require an ancillary unit ACE2 that is a molecular target for the spike protein of the SARS-CoV-2 virus. SLC6A19 has been proposed as a molecular target for the treatment of metabolic disorders resembling gastric surgery bypass. Inhibition of SLC6A15 appears to have a promising outcome in the treatment of psychiatric disorders. SLC6A19 and SLC6A20 have been suggested as potential targets in the treatment of COVID-19. In this review, we gathered recent advances on orphan transporters, their structure, functions, related disorders, and diseases, and in particular their relevance as therapeutic targets.

中文翻译：

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SLC6A15–SLC6A20 中性氨基酸转运蛋白亚家族：功能、疾病及其治疗相关性


中性氨基酸转运蛋白亚家族由六个成员组成，依次为 SLC6A15-SLC620，也称为孤儿转运蛋白，代表膜、钠依赖性同向转运蛋白，属于溶质载体 6 (SLC6) 家族。主要是，它们利用膜电位作为驱动力介导中性氨基酸从细胞外环境向细胞或储存囊泡的运输。孤儿转运蛋白广泛分布于全身各处，覆盖多个系统；例如，中枢神经、肾脏或肠道系统，将细胞提供为用于生化、信号传导和随后建立通路的分子。它们负责氨基酸的肠道吸收和肾脏重吸收。在中枢神经系统中，孤儿转运蛋白构成了提供神经递质前体的重要介质。与上述转运蛋白相关的疾病凸显了其重要性； SLC6A19 突变与代谢性 Hartnup 疾病相关，而 SLC6A15 表达的改变与抑郁/压力相关疾病相关。 SLC6A18-SLCA20 突变导致亚氨基甘氨酸尿和/或高甘氨酸尿。 SLC6A18-SLC6A20 要到达细胞膜，需要一个辅助单元 ACE2，它是 SARS-CoV-2 病毒刺突蛋白的分子靶标。 SLC6A19 已被提议作为治疗代谢性疾病（类似于胃旁路手术）的分子靶点。抑制 SLC6A15 似乎在精神疾病的治疗中具有良好的效果。 SLC6A19 和 SLC6A20 已被建议作为治疗 COVID-19 的潜在靶点。 在这篇综述中，我们收集了孤儿转运蛋白、其结构、功能、相关疾病和疾病的最新进展，特别是它们作为治疗靶点的相关性。