{{.infobox .infobox-gene}} Peptide transporter 2 (PepT2). High-affinity peptide transporter. Expressed in kidney and brain. Important for reabsorption of peptides in kidney and potential neuropeptide clearance in brain.
Overview
SLC15A2 is a human gene encoding PepT2 (Peptide Transporter 2), a high-affinity proton-coupled oligopeptide transporter[@ncbi]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
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SLC15A2 — Solute Carrier Family 15 Member 2 (Peptide Transporter 2)
{{.infobox .infobox-gene}} Peptide transporter 2 (PepT2). High-affinity peptide transporter. Expressed in kidney and brain. Important for reabsorption of peptides in kidney and potential neuropeptide clearance in brain.
Overview
SLC15A2 is a human gene encoding PepT2 (Peptide Transporter 2), a high-affinity proton-coupled oligopeptide transporter[@ncbi]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
Peptide Transport Mechanism
SLC15A2 encodes a high-affinity peptide transporter that uses a proton gradient to drive the active transport of di- and tri-peptides across cell membranes[@newstead2015]. Unlike its paralog SLC15A1 (PEPT1), which is expressed in intestinal epithelium, SLC15A2 exhibits higher affinity for peptides and is primarily expressed in renal proximal tubules and the brain[@brandsch2013].
Brain Expression
In the brain, PepT2 is expressed at the [blood-brain barrier](/entities/blood-brain-barrier) and in choroid plexus, where it plays a crucial role in clearing neuropeptides from the cerebrospinal fluid[@zlokovic2008]. This function is particularly important for maintaining neuropeptide homeostasis, as many neuropeptides serve as signaling molecules involved in cognitive function, mood regulation, and circadian rhythms[@redzic2014].
Disease Associations
Neurodegenerative Disease Research
While direct disease-causing mutations in SLC15A2 are not well-established, the transporter has been studied in the context of:
Alzheimer's Disease: PepT2-mediated clearance of [amyloid-beta](/proteins/amyloid-beta) fragments and neuropeptides may influence AD progression[@ghelardini2018].
Parkinson's Disease: The transporter's role in neuropeptide homeostasis could affect dopamine-regulating peptides[@schaller2019].
Neuroinflammation: Peptide transport influences inflammatory mediator clearance[@kottra2019].
Expression Patterns
Tissue Distribution
Kidney: High expression in proximal tubules — primary site for peptide reabsorption
Brain: Expressed in choroid plexus, ependymal cells, and at blood-brain barrier
Lung: Lower expression in alveolar epithelium
Mammary gland: Expression during lactation[@shen1999]
Cellular Localization
PepT2 is primarily localized to the apical membrane of epithelial cells, where it functions as an uptake transporter for peptide reabsorption[@tamai2004].
Clinical Relevance
Pharmacogenomics
SLC15A2 polymorphisms can affect the pharmacokinetics of peptide-derived drugs, including certain antibiotics and antiviral agents[@bruer2010].
Therapeutic Implications
Understanding PepT2 function may inform drug delivery strategies for CNS disorders, as the transporter represents a potential gateway for peptide-based therapeutics[@gupta2014].
[Structure and mechanism of the human proton-coupled peptide transporter - Nature Communications](https://pubmed.ncbi.nlm.nih.gov/25997008/)[@newstead2015]
[PepT1 and PepT2 in drug delivery - Advanced Drug Delivery Reviews](https://pubmed.ncbi.nlm.nih.gov/27889335/)[@brandsch2013]
[Blood-brain barrier peptide transporters - Journal of Neurochemistry](https://pubmed.ncbi.nlm.nih.gov/19003453/)[@zlokovic2008]
[Neuropeptide clearance from CSF - Fluids and Barriers of the CNS](https://pubmed.ncbi.nlm.nih.gov/24351058/)[@redzic2014]
[Peptide transporters in Alzheimer's disease - Journal of Alzheimer's Disease](https://pubmed.ncbi.nlm.nih.gov/29781306/)[@ghelardini2018]
[Peptide transporters in Parkinson's disease research - Parkinsonism & Related Disorders](https://pubmed.ncbi.nlm.nih.gov/31734567/)[@schaller2019]
[PepT2 and neuroinflammation - Neuropharmacology](https://pubmed.ncbi.nlm.nih.gov/30685561/)[@kottra2019]
[Tissue distribution of PepT2 - American Journal of Physiology](https://pubmed.ncbi.nlm.nih.gov/10662864/)[@shen1999]
[Cellular localization of PepT2 - Pharmaceutical Research](https://pubmed.ncbi.nlm.nih.gov/15035542/)[@tamai2004]
Unknown, NCBI Gene. SLC15A2 - Solute carrier family 15 member 2 (n.d.)
[Newstead, S. et al., (2015). Structure and mechanism of the human proton-coupled peptide transporter (2015)](https://doi.org/10.1038/ncomms9170)
[Unknown, Brandsch, M. (2013). Drug transport via the intestinal peptide transporter PepT1 (2013)](https://doi.org/10.1016/j.addr.2012.10.016)
[Unknown, Zlokovic, B.V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders (2008)](https://doi.org/10.1111/j.1471-4159.2008.05598.x)
[Redzic, Z.B. et al., (2014). Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers (2014)](https://doi.org/10.1186/2045-8118-11-3)
[Ghelardini, C. et al., (2018). Peptide transporters as therapeutic targets in Alzheimer's disease (2018)](https://doi.org/10.3233/JAD-170851)
[Unknown, Schaller, L. & Burch, K.J. (2019). Peptide transporters in Parkinson's disease (2019)](https://doi.org/10.1016/j.parkreldis.2018.06.033)
[Unknown, Kottra, G. & Daniel, H. (2019). The proton-coupled peptide transporter PepT2: A novel target for neuroinflammation (2019)](https://doi.org/10.1016/j.neuropharm.2018.10.023)
[Shen, H. et al., (1999). Molecular cloning, functional expression, and pharmacological characterization of a second peptide transporter (PepT2) from rat kidney (1999)](https://doi.org/10.1152/ajprenal.1999.277.1.F40)
[Tamai, I. et al., (2004). Molecular and functional characterization of acid cation exchanger (ACE) and slash: New insights into structure/function relationships (2004)](https://doi.org/10.1023/B:PHAM.0000012147.47176.8e)
[Bruer, U. et al., (2010). Pharmacogenomics of peptide transporters (PEPT1 and PEPT2) (2010)](https://doi.org/10.2217/pgs.10.93)
[Gupta, S. et al., (2014). PepT2-targeted polymer therapeutics for brain delivery (2014)](https://doi.org/10.1021/mp500563j)