Abstract: Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that ensheath nearby axons to support action potential propagation and axon metabolism. Myelination involves the rapid production of lipid-rich membrane, compaction of the multilamellar myelin sheath, and the resultant restriction of cytoplasm to non-compact compartments. During myelination, septate-like junctions form between the axon and lateral cytoplasmic endings of the myelin sheath at a specialized domain called the paranode (Figure 1A). Cytoplasm-filled loops at the paranode (hereon referred to as paranodal loops) host a network of organelles, but their regulation and function are poorly understood. Until recently, it was not at all clear how molecules from the oligodendrocyte cell body were transported across the compacted layers of the myelin sheath to access the cytoplasmic growing edge. In 2014, cytoplasmic channels that traverse the compact myelin sheath were identified in the CNS (Snaidero et al., 2014), opening the door to investigate the function and regulation of the organelles contained within these specialized cytoplasmic compartments. Further, it was shown that active mitochondria in non-compact myelin contribute to the generation of calcium transients that appear to regulate internode remodeling (Battefeld et al., 2019), supporting a functional link between mitochondria and myelin remodeling.