The effects of Sox21 gene deletion on hair lipids have been studied. For the cuticle-specific bound lipid 18-methyl eicosanoic acid (18-MEA), which was found to predominantly exist as the free form in Sox21(-/-) hair, total levels and distribution were unexpectedly unchanged. This indicates that while the biosynthesis of 18-MEA is unaffected, its covalent attachment to the cuticle surface is disrupted by loss of keratin-associated protein binding partners. Although the class compositions differed, the total ceramide (CER) levels were found to be comparable between Sox21(+/+) and Sox21(-/-) hairs. Deletion of the gene was also found to increase cholesterol sulphate (CS) levels. The biosynthesis process might be associated with cuticle keratinocyte maturation, because both CS and CERs are known bioactives in keratinocyte differentiation.