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Roles of sensory receptors in non-sensory organs: the kidney and beyond

Nature Reviews Nephrology volume 21, pages 253–263 (2025)Cite this article

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Abstract

Olfactory receptors (ORs), taste receptors and opsins are well-known for their pivotal roles in mediating the senses of smell, taste and sight, respectively. However, in the past two decades, research has shown that these sensory receptors also regulate physiological processes in a variety of non-sensory tissues. Although ORs, taste receptors and opsins have all been shown to have physiological roles beyond their traditional locations, most work in the kidney has focused on ORs. To date, renal ORs have been shown to have roles in blood pressure regulation (OLFR78 and OLFR558) and glucose homeostasis (OLFR1393). However, sensory receptors remain drastically understudied outside of traditional sensory systems, in part because of inherent challenges in studying these receptors. Increased knowledge of the physiological and pathophysiological roles of sensory receptors has the potential to substantially improve understanding of the function of numerous organs and systems, including the kidney. In addition, most sensory receptors are G protein-coupled receptors, which are considered to be the most druggable class of proteins, and thus could potentially be exploited as future therapeutic targets.

Key points

  • Olfactory receptors (ORs), taste receptors and opsins have functional roles in non-sensory organs and tissues, including in the kidney, lungs, testis, spinal cord, adipose tissue, vasculature and immune system.

  • Studies of ORs are challenging but use of best practices in the field enable these important receptors to be interrogated in a rigorous fashion.

  • ORs have roles in sperm chemotaxis, macrophage chemosensation and migration, and lung vasodilation; taste receptors modulate lung vasodilation and sense pH changes in cerebrospinal fluid; and opsins have been reported to have roles in adipose tissue function and thermogenesis.

  • In the kidney, Olfr78 is expressed in blood vessels; activation of this OR in the renal afferent arteriole increases renin release.

  • Olfr558 localizes to blood vessels, including the renal afferent arteriole, and is required for sex differences in blood pressure.

  • Olfr1393 is expressed in the renal proximal tubule, where it modulates sodium–glucose cotransporters, resulting in effects on glucose tolerance.

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Fig. 1: OLFR78 and renin release.
Fig. 2: OLFR558 and blood pressure.
Fig. 3: OLFR1393 and glucose handling.

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Acknowledgements

We are grateful for support from the American Heart Association Career Development Award (23CDA1050485 to J.X.), the Dekkers Endowed Chair in Human Science (Georgetown University, to B.D.S.), R03TR004193 (NIH/NCATS to B.D.S.), American Heart Association Established Investigator Award (to J.L.P.), R21AG081683 (to J.L.P.), R01DK137762 (to J.L.P.), and R01DK139021 (to J.L.P.).

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  1. Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Jiaojiao Xu & Jennifer L. Pluznick

  2. Department of Human Science, Georgetown University, Washington, DC, USA

    Blythe D. Shepard

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All authors researched data for the article, contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Jennifer L. Pluznick.

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Under a licensing agreement between Firmenich and the Johns Hopkins University, the University, B.D.S., and J.L.P. are entitled to fees associated with an invention described in this article (the Lucy tag; patent US 9783585; BE 2893020; DE 2893020; CH 2893020). This arrangement has been reviewed and approved by the Johns Hopkins University and Georgetown University in accordance with its conflict of interest policies.

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Xu, J., Shepard, B.D. & Pluznick, J.L. Roles of sensory receptors in non-sensory organs: the kidney and beyond. Nat Rev Nephrol 21, 253–263 (2025). https://doi.org/10.1038/s41581-024-00917-y

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