The UNC5H family of proteins act as transmembrane receptors for netrin-1 and play a crucial role in axon guidance and migration of neural cells. Additionally, when cleaved by a caspase to produce an intracellular fragment containing a death domain,UNC5H receptors induce apoptosis. This activity is blocked by the binding of netrin-1. In the absence of netrin-1, UNC5H receptors act as tumor suppressors by inhibiting anchorage-independent growth and invasion, but mutation of these receptors provides a potential mechanism for tumorigenicity. The expression of UNC5H receptors is down-regulated in multiple carcinomas, including colorectal, breast, ovary, uterus, stomach, lung, and kidney cancers. UNC5H4, also known as UNC5D (unc-5 homolog D), is single-pass type I membrane protein that is a member of the UNC5H netrin receptor family. Two isoforms of UNC5H4 exist due to alternative splicing events.

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