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Objective: Lip skin dryness and chapping are major concerns related to lip skin care in many populations. The distinctive features of lip skin, such as the low water-holding capacity and weak skin barrier, are strongly associated with these problems; however, few studies have examined lip skin characteristics and the mechanisms underlying these issues. This study was conducted to identify the biophysical properties of dry lip skin and molecular targets affecting lip skin physiology., Methods: Skin hydration, transepidermal water loss and lip skin scaling were evaluated in 40 female subjects. Skin scaling was assessed as a percentage area divided into five categories (G0, G1, G2, G3 and G4) according to the thickness level of tape-stripped corneocytes. The activities and amounts of proteases, cathepsin D and bleomycin hydrolase were measured as markers for the desquamation process and skin hydration, respectively., Results: Skin hydration showed a significantly positive correlation with the percentage area of evenly thin corneocytes (G0) and negative correlations with the percentage areas of slightly thick to severely thick corneocytes (G1-G4). The corneocyte unevenness ratio (CUR) was calculated by dividing the sum of the G1, G2, G3 and G4 values with the G0 value. The CUR was significantly negatively correlated with skin hydration, suggesting that CUR is a new parameter representing the severity of lip scaling. Subjects with lower hydration and higher CUR had higher bleomycin hydrolase activity and lower cathepsin D activity, respectively, than subjects with higher hydration and lower CUR., Conclusion: Our study revealed a correlation between lip skin hydration and severity of lip scaling and verified the association of protease activity with the hydration and chapping state of lip skin. These observations provide a basis for further studies of the persistent problem of lip skin dryness and chapping., (© 2021 LG Household & Healthcare .International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)