Netrin proteins are a family of laminin-related secreted proteins that provide guidance signals for axonal growth and cell migration during development. Netrin signaling is dependent on the concentration of calcium outside the cell and the level of PKA activity. In axonal cells, a reduction in PKA activity converts the responsiveness of the axons to the netrin proteins, as the cells are repelled, rather than attracted, by the netrin gradient. Netrin-4 is related to the Laminin ∫ chains, and is therefore also designated ∫-netrin. It is present in the basement membranes of the vasculature, lateral olfactory tract, kidney and ovary. In humans, the gene encoding for the netrin-4 protein is localized to chromosome 12q22-q23. High levels of netrin-4 mRNA have also been detected in many cells and tissues, including cerebral cortex, hippocampus, amygdaloid nuclei and Purkinje cells. Netrin-4 is important in neural, kidney and vascular development.