One hundred and fifty years ago, Johann Thudichum described sphingolipids as unusual “Sphinx-like” lipids from the brain. Today, we know that thousands of sphingolipid molecules mediate many essential functions in embryonic development and normal physiology. In addition, sphingolipid metabolism and signalling pathways are dysregulated in a wide range of pathologies, and therapeutic agents that target sphingolipids are now used to treat several human diseases. However, our understanding of sphingolipid regulation at cellular and organismal levels and their functions in developmental, physiological and pathological settings is rudimentary. In this Review, we discuss recent advances in sphingolipid pathways in different organelles, how secreted sphingolipid mediators modulate physiology and disease, progress in sphingolipid-targeted therapeutic and diagnostic research, and the trans-cellular sphingolipid metabolic networks between microbiota and mammals. Advances in sphingolipid biology have led to a deeper understanding of mammalian physiology and may lead to progress in the management of many diseases.

150 年前，Johann Thudichum 将鞘脂描述为来自大脑的不寻常的“狮身人面像状”脂质。今天，我们知道数以千计的鞘脂分子介导胚胎发育和正常生理学中的许多基本功能。此外，鞘脂代谢和信号通路在多种病理中失调，靶向鞘脂的治疗剂现在用于治疗多种人类疾病。然而，我们对细胞和生物体水平的鞘脂调节及其在发育、生理和病理环境中的功能的理解是初级的。在这篇综述中，我们讨论了不同细胞器中鞘脂途径的最新进展、分泌的鞘脂介质如何调节生理学和疾病、鞘脂靶向治疗和诊断研究的进展，以及微生物群和哺乳动物之间的跨细胞鞘脂代谢网络。鞘脂生物学的进步使人们对哺乳动物生理学有了更深入的了解，并可能导致许多疾病管理的进步。