While studies in asebia-2J (Scd1(ab2J)) mice [8] showed that sebaceous lipids are not required for permeability barrier function [9], others have documented several important roles for SG and SG secretions. Pertinently, barrier function remains intact in the hair follicle down to the entry point of the duct draining SG, while the hair follicle epithelium above that level can regenerate a fully functional barrier [10]. Yet, function deteriorates immediately below that level, as demonstrated with electron dense tracers [9]. As noted above, reductions in SG secretions precipitate scarring alopecia in humans [11], indicating important lubricating properties that facilitate the outward migration of hair follicles.

Several decades ago, researchers sought the origins of the skin’s antirachitic properties in furred rodents [12]. While urine, feces, and other bodily secretions failed to reveal activity, testing of a greasy material, adherent to the animals’ wire cages, exhibited the sought-after activity, providing the initial evidence that SG secretions could deliver vitamin D (VD3) to the surface of furred animals’ skin. Though the fur of most mammals blocks incident UV-B from reaching the epidermis, VD3-laden, SG secretions can bypass this restriction. Accordingly, much of the ‘social grooming’ that occurs in furred animals includes licking of each other’s skin surface, likely resulting in the ingestion of substantial VD3 (though not applicable to humans, here we record a second important function for SG – delivery of VD3 to the skin surface of hairy mammals, where it subsequently can be ingested).

In contrast, incident UV-B readily breaches the epidermis of sparsely haired, modern humans, quickly converting the distal cholesterol precursor, 7-dehydrocholesterol (7DHC) into pre-VD3 [13], followed by its thermal conversion to VD3. In geographic regions of northern Europe, where little UV-B irradiation penetrates the atmosphere, loss-of-function (LOF) mutations in the enzyme, 7-dehydrocholesterol reductase, become relatively common in affected humans, ensuring that 7DHC remains available for photoconversion [14, 15]. These northern-dwelling humans also frequently display LOF mutations in the gene encoding filaggrin, which after distal proteolysis and deimination yields trans-urocanic acid, the most potent UV-B photophore in human skin [16], further assuring that incident UV-B will penetrate deep into the nucleated layers of the epidermis (11), where VD3 is generated. Indeed, because we humans generate abundant vitamin D (VD3) in our epidermis, the cholesterol biosynthetic pathway in SG aborts distal to the formation of squalene in service to metabolic conservation.

Our studies in asebia mice yielded insights into yet another function of SG – hydration of the stratum corneum (SC). We found evidence of considerable lipase activity in SG, which if active, would hydrolyze sebum-derived tri- and diglycerides not only into free fatty acids [17], but also into glycerol, a potent endogenous humectant. This conjecture is consistent with the observation that SG-enriched skin sites, like the forehead and upper torso, exhibit elevated SC hydration [18]. This finding brings us up to three important functions of SG – prevention of scarring alopecia, VD3 delivery to the surface of hairy skin, and tissue hydration.

Returning to the lipolysis of glycerolipids in SG, consider that not only glycerol, but also abundant free fatty acids (FFA) are formed, which join epidermis-derived FFA following the hydrolysis of phospholipids in epidermal terminal differentiation [19]. These species are antimicrobial for several reasons, including their ability to destroy microbial pathogens in a chain-length dependent fashion, and their acidity, which is inimical to the growth of gram-positive pathogens. In contrast, that same low pH favors the colonization of human skin by its normal cutaneous flora. The addition of antimicrobial activity adds yet another (fourth) positive attribute of SG products.

In response to the many free radicles and pollutants in the environment, the epidermis (but not SG) generates a suite of antioxidant species, including glutathione reductase, thioredoxin reductase, superoxide dismutase, and catalase. Notably, this list does not include vitamin E (VitE), which instead is delivered to the skin surface via SG secretions. Once absorbed into the epidermis, VitE is metabolized by cytochrome p450 isoforms into a suite of additional tocopherols and tocotrienols, which in turn activate PPARγ [20]. The latter exhibits potent anti-inflammatory activity, accounting for the benefits of PPARγ analogues in the treatment of diverse inherited and acquired inflammatory disorders [21, 22]. Yet, whether VitE secretion is impacted by factors that regulate SG structure and secretion, such as androgens and their estrogen metabolites, or retinoids, remains unknown. Nonetheless, the delivery of VitE and other downstream, bioactive lipids to the skin surface illustrates yet another (fifth) important function of SG.

In a recent review article, Christos Zouboulis and his associates reviewed the negative impact of sebaceous lipids on perifollicular and dermal innate immune responses. The pathophysiological consequences, of course, include the provocation of acne, but extend to other inflammatory dermatoses, including seborrheic dermatitis and atopic dermatitis [1]. Hence, because of these apparently negative consequences of SG activity, we have chosen not to include these activities among the positive attributes of SG.

From this point onward, cataloguing further benefits of SG secretions becomes more nebulous. Most controversial is the subject of pheromones in human biology. Pheromones are volatile, species-specific substances that have been implicated, though not yet proven to impact reproductive instincts in humans. Indeed, some authors doubt whether they play any role in human reproduction. Much more certain is a role for pheromones in earthworm reproduction [23]. Consider however that SG secretions, along with apocrine gland secretions, generate multiple volatile compounds that are odorants, including some that could function as pheromones [24]. Charles Darwin has been credited with the initial observation that when animals secrete odiferous secretions, they strongly signal reproductive responses [25]. Though our nasal passages display multiple odorant receptors, whether these structures also recognize and respond to pheromones remains unknown.

The authors have declared that no competing interests exist.

The author declares no clinical trials were used in the present study.

The author declares that no experiments on humans or human tissues were performed for the present study.

The author declares that no informed consent was obtained from any humans, donors, or donors’ representatives participating in the study.

The author declares that no experiments on animals were performed for the present study.

The author declares that no commercially available immortalized human and animal cell lines were used in the present study.

No use of AI was reported.

No funding was reported.

PME reviewed literature and conceptualized and wrote the manuscript. JSW edited the manuscript.