Abstract: The Hedgehog (HH) family includes Indian (IHH), Desert (DHH), and Sonic Hedgehog (SHH). Proteins of the HH family are distinguished by their function as morphogens, i.e., molecules that regulate the pattern of tissue development in accordance with concentration gradient. Data accumulated over the years clearly demonstrate that HH signaling is essential in myelination, particularly in the life cycle of the oligodendrocyte lineage. DHH is a key factor for Schwann cell function in the myelination of the peripheral nervous system and IHH is directly involved in the specification of oligodendrocyte precursor cells (OPCs) at least in the zebrafish. The most studied family member in central nervous system (CNS) myelination is SHH. SHH signaling has been identified as a crucial component in oligodendrocyte differentiation and remyelination (Russo et al., 2024). SHH is synthetized as a 46 kDa precursor protein which undergoes an autoproteolytic cleavage producing the excision of 19 kDa amino-terminal region (HH-N) and SHH carboxy-terminal polypeptide. The HH-N domain binds cholesterol and palmitic acid producing a functional signaling molecule.