Semaphorins represent a large family composed of 19 secreted, GPI-linked or transmembrane members divided into 5 classes (3 to 7) and characterized by the presence of a 500 amino acid Sema domain in the N-terminus. Initially described for their role in axon guidance and apoptosis during neuronal development, some semaphorins like the class 4, regulate immune functions and are involved in organogenesis and angiogenesis. The transmembrane class 6 semaphorins include 4 members (SEMA6A to 6D). SEMA6A features an intracellular binding site for regulatory Evl protein. In the immune system, SEMA6A protein is restricted in vitro and in vivo to an activation status of Langerhans cells.