The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.

皮肤的屏障功能主要位于皮肤的最外层角质层（SC）。SC 由死细胞组成，细胞间隙中具有高度组织化的脂质片层。由于脂质基质形成唯一的连续途径，因此脂质在化合物通过 SC 的渗透中发挥着重要作用。主要脂质类别是神经酰胺 (CER)、胆固醇 (CHOL) 和游离脂肪酸 (FFA)。SC 脂质基质的分析对于了解皮肤屏障功能至关重要，不仅在健康皮肤中，而且在皮肤屏障受损的炎症性皮肤病中也是如此。在这篇综述中，我们提供了 i) 为获取健康皮肤和炎症性皮肤病 SC 中脂质成分和组织信息而采取的步骤的历史概述，ii) 有关 CER、CHOL 和 FFA 在脂质相行为中所起作用的信息非常复杂的脂质模型系统的知识，以及如何利用这些知识来理解炎症性皮肤病中脂质相行为的偏差，iii) 关于 CER 亚类和链长分布对脂质组织和脂质膜渗透性的作用的知识具有合成 CER、CHOL 和 FFA 的复杂和简单模型系统，iv) 不同物种和复杂模型系统的 SC 中脂质相行为的相似性，以及 vi) 调节脂质成分的未来方向，有望改善炎症皮肤的皮肤屏障疾病。