Netrins/UNC-6 (netr: Sanskrit for “one who guides”) are a family of laminin-related small proteins that are involved in neurite outgrowth and axon guidance. Netrins bind to the DCC and UNC5 family of receptors to attract or repel axons. Mouse Netrin-G1a is synthesized as a 539 amino acid (aa) precursor with an 18 aa signal sequence, a 399 aa laminin-related region containing an N-terminal laminin globular domain (domain VI) followed by 3 laminin EGF-like repeats, and a 122 aa C domain with a hydrophobic signal for glycosyl phosphatidylinositol (GPI) lipid linkage. Unlike classical Netrins which have a C domain rich in basic aa residues that serves as a heparin binding site, Netrin-G1a is predominantly anchored on the cell surface via GPI linkages. By alternative splicing, at least six isoforms for Netrin-G1 have been identified. All G1a variants (G1b through G1f) are shorter than G1a and lack one or more of the EGF-like domains. Mouse Netrin-G1a shares 27%, 26% and 31% aa sequence identity with mouse Netrins-1, 3 and 4, respectively. It also shares 60% aa identity with another GPI-anchored mouse Netrin-G2a. Although a human homolog of mouse Netrin-G1a has not been reported, a human G1f that shares 97% aa sequence identity with mouse G1f has been cloned. Netrin-G1 has widespread expression, occurring in olfactory mitral cells, cells of the inferior colliculus (hearing), dorsal thalamus (behavior), and cells of the deep cerebellar nuclei and inferior olive (motion). The G-type Netrins are found only in vertebrates and are suggested to play a role in forming circuits associated with motor activity. Conditioned media containing myc-tagged Netrin-G1a proteins did not bind to cells transiently transfected with the Netrin receptors DCC, UNC5H1, UNC5H2, or UNC5H3 (1 - 4).