Receptor · Melanocortin 5 receptor

MC5R — the exocrine receptor

The least understood of the five, but with a clear signature role: regulating exocrine glands, most notably the sebaceous glands that oil skin and fur.

By melanocortin.com editorialLast updated 2026
Tissue
Exocrine glands (sebaceous, lacrimal); immune cells
Ligands
α-MSH, ACTH
Function
Regulates exocrine secretion — notably sebum and lipid production — and contributes to immune modulation.
When it fails
Knockout models show defective sebaceous secretion and altered thermoregulation; human role still being mapped.

MC5R is the melanocortin family's generalist. Its messenger RNA shows up in a strikingly wide range of tissues, which long made its core function hard to name. The answer came from removing it: the defining role of MC5R is the control of exocrine glands.[1]

The sebum signal

When the Mc5r gene is knocked out in mice, the animals develop a severe defect in water repulsion and thermoregulation, traced to reduced production of sebaceous lipids — the oily secretion that waterproofs fur and skin. The knockout also impairs other exocrine tissues, including the Harderian, lacrimal, and preputial glands, implying that one receptor coordinates secretion across several gland types.[2] Mechanistically MC5R behaves like its relatives — coupling to Gs and raising cyclic AMP — with α-MSH and ACTH as agonists.[3]

From mouse to human

Because the sebaceous role is so clean in mice, MC5R is of interest in human skin biology — for example in the regulation of sebum and the differentiation of sebaceous glands, with relevance to conditions such as acne. Beyond skin, MC5R has been linked to immune modulation and to lipid handling in other tissues, though its full human physiology is still being mapped and is less settled than that of MC1R or MC4R.[3] Where the science is genuinely unresolved, this page says so rather than overstating it.

For how MC5R fits the broader system, see theoverview pillar; the related skin receptor isMC1R.

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References

  1. 1.Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 27(7):736–49. 2006. link ↗
  2. 2.Chen W, Kelly MA, Opitz-Araya X, et al. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell. 91(6):789–98. 1997. link ↗
  3. 3.Rodrigues AR, Almeida H, Gouveia AM. Melanocortin 5 receptor signaling pathway in health and disease. Review (PMC7511443). 2020. link ↗