UNC5H2/UNC5B is a transmembrane molecule that mediates axon repulsion and growth cone collapse through interactions with Netrin, Neogenin, and FLRT3. Its association with DCC switches the DCC-Netrin-1 response from attraction to repulsion. Outside the nervous system, UNC5H2 facilitates Netrin-1-mediated inhibition of capillary branching and leukocyte migration as well as Netrin-1-mediated promotion of osteoclast differentiation. It is downregulated in multiple cancers and inhibits tumor cell growth and invasion. It also plays a critical role in the development of atherosclerosis and the survival of renal tubular epithelial cells during acute kidney injury.