刺猬信号通路在胚胎组织形态建模、后胚胎组织再生和癌症方面发挥着至关重要的作用，然而刺猬信号传递和接受的某些方面直到最近仍然不清楚。生化和结构研究惊人地揭示了脂质在刺猬信号中发挥的核心作用。信号—刺猬蛋白—在其生物合成过程中由胆固醇和棕榈酸修饰，因此需要专门的蛋白质如运输蛋白Dispatched和几种脂质结合的载体进行细胞外分泌和受体结合。另外的脂质转换介导对刺猬信号的响应，包括甾醇激活传导蛋白Smoothened。甾醇进入Smoothened的通路受到表观甾醇转运蛋白和刺猬受体Patched的调节，其活性被刺猬结合所阻止。除了这些以脂质为中心的机制及其在药理学通路调节中的相关性，我们还讨论了刺猬途径活性在干细胞或它们的细胞种植体中的新兴作用，并探讨了其对损伤或疾病组织再生和修复的转化意义。©2023. Springer Nature 有限公司。

The Hedgehog signalling pathway has crucial roles in embryonic tissue patterning, postembryonic tissue regeneration, and cancer, yet aspects of Hedgehog signal transmission and reception have until recently remained unclear. Biochemical and structural studies surprisingly reveal a central role for lipids in Hedgehog signalling. The signal - Hedgehog protein - is modified by cholesterol and palmitate during its biogenesis, thereby necessitating specialized proteins such as the transporter Dispatched and several lipid-binding carriers for cellular export and receptor engagement. Additional lipid transactions mediate response to the Hedgehog signal, including sterol activation of the transducer Smoothened. Access of sterols to Smoothened is regulated by the apparent sterol transporter and Hedgehog receptor Patched, whose activity is blocked by Hedgehog binding. Alongside these lipid-centric mechanisms and their relevance to pharmacological pathway modulation, we discuss emerging roles of Hedgehog pathway activity in stem cells or their cellular niches, with translational implications for regeneration and restoration of injured or diseased tissues.© 2023. Springer Nature Limited.