ROS1 is a receptor tyrosine kinase (RTK) involved in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. It activates downstream signaling pathways related to differentiation, proliferation, growth and survival such as the PI3 kinase-mTOR signaling pathway. ROS1 mediates the phosphorylation of PTPN11, an activator of this pathway. It phosphorylates and activates the transcription factor STAT3 to control anchorage-independent cell growth. Furthermore, ROS1 mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. Some lung adenocarcinomas, glioblastomas, ovarian carcinomas and other cancers express ROS1 fusion proteins that result from genomic rearrangements, and they can sometimes be treated successfully with inhibition therapies. In immunohistochemistry, ROS1 has membranous positivity in the brain, lung, and epididymis. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Clinical Cancer Research. 19 (15): 4040–5, PMID: 23719267;