RTN4 and breast cancer: GJB2 has previously been identified as a gene with prognostic significance in brain,68,69 pancreatic70,71 and breast cancer.72 RTN4 has two long (32 aa) transmembrane domains and the region between these domains (NOGO-66) has been shown to mediate protein interaction with cells expressing RTN4 receptors.87,88 The long transmembrane domains have been also postulated to confer distinct topological organisations of this protein, particularly exposing the N-terminus (the more divergent domain between RTN proteins) extracellularly.