Tunneling nanotubes in the nervous system: The fourth pillar of brain connectivity

Tunneling nanotubes (TNTs) are thin, actin-based membranous conduits that enable direct and indirect cytoplasmic exchange between distant cells. Once considered a rare in vitro phenomenon, TNTs are increasingly recognized as dynamic intercellular communication routes in the central nervous system. Here, we discuss emerging evidence supporting the presence and functional relevance of TNTs in the brain, their roles in physiological coordination and pathological spread, and the conceptual shift they demand in how we understand neural connectivity. We argue that TNTs represent a previously underappreciated layer of brain organization-one that may critically shape neurodegeneration, neuroinflammation, and repair-and outline key experimental and theoretical directions to move the field forward.