Deleted in colorectal cancer (DCC, chromosome 18q21) was originally identified as a putative tumor suppressor gene that is lost in more than 70% of colorectal cancers. The gene has also been deleted in several other types of cancer. The DCC protein is a type I transmembrane glycoprotein that belongs to the immunoglobulin (Ig) superfamily. The extracellular domain is composed of four Ig like domains and six fibronectin type III repeats. Native DCC is found in three isoforms. Two forms, a long and a short isoform, are produced from the same gene but have different initiation sites. The third isoform, produced by alternative splicing, is expressed only in embryonic tissue. Mouse DCC extracellular domain shares 97% and 99% homology with human and rat DCC extracellular domains, respectively. In adults, DCC is highly expressed in the brain but is also expressed at very low levels in multiple normal tissues. In the embyro, high levels of expression are detected in the brain and neural tube. DCC functions as a receptor or a component of a receptor for netrins and mediates the effects of netrins on commissural axons. Netrins are chemoattractants responsible for the guidance of commissural axons at the midline and of motor axons to the their target muscles. DCC induces apoptosis in the absence of ligand binding, blocks apoptosis when engaged by netrin 1, and also acts as a caspase substrate.