(a) Chemical structure of C16:0-Cer, with color-coded sphingoid base (black) and N-acyl chain (red). (b) Chemical structures of clickable and photoswitchable ceramides caCer-1–4. (c) Chemical structures of clickable ceramide cCer and photoswitchable ceramide ACe-1. (d) caCer-1 undergoes reversible isomerization between its cis- and trans-configuration with UV-A (365 nm) and blue (470 nm) light, respectively. (e) Chemical synthesis of the photoswitchable sphingoid base aSph-1, which was N-acylated with a terminal alkyne-functionalized C15 fatty acid to afford caCer-3. (f) UV-Vis spectra of the red-shifted variant caCer-3 (50 μM in DMSO) in its dark-adapted (trans, black), UV-A-irradiated (cis, violet) and blue-irradiated (trans, blue) states. (g) caCer-3 (50 μM in DMSO) undergoes isomerization to its cis-configuration with UV-A light (350–390 nm), and this effect is completely reversed with blue light (465 nm). Photoswitching was monitored by measuring the absorbance at 365 nm.