Critically, it was shown that ZDHHC3-Cadm4 signaling is tightly involved in neuroinflammation in different models of demyelination diseases (LPS/EAE/LPC, Fig. 7 and Supplementary Figs. 7–10), emphasizing not only the key roles of ZDHHC3-Cadm4 axis for myelination but also a conserved pathological mechanism for varied demyelination diseases (Fig. 8a). Here, ZDHHC3 is linked to demyelinating disease.