The membranes of myelinating Schwann cells are joined by tight, gap and adherens junctions, all of which are found in regions of noncompact myelin: the paranodal loops, incisures of Schmidt-Lanterman and mesaxons. Tight junctions help establish polarity in mammalian epithelia by forming a physical barrier that separates apical and basolateral membranes. Pals-associated tight junction protein (PATJ), the human homolog of Drosophila Discs Lost, is differentially localized in myelinating Schwann cells. PATJ associates with Claudin-1, CRB1 (a transmembrane protein that plays a role in epithelial cell polarity and photoreceptor development), and Pals1 (a Lin-7 associated protein). The PATJ/Pals1/CRB1 complex can form a tripartite tight junction in epithelial cells crucial to their integrity.