A number of leucine-rich repeat proteins with LRRs and Ig regions, which seem to serve similar functions, have been found to be expressed predominantly in cells of nervous tissues [
8,
16,
17], and are involved in the differentiation and development of normal nervous tissues [
1,
2]. LRRC4C/NGL-1, LRRC4/NGL-2 and LRRC4B/NGL-3 share the same domain structure. The structure character of LRRC4s implies that these genes might be involved in the development and differentiation of the nervous system. LRRC4C/NGL-1 was first identified as a ligand for netrin-G1 [
8]. LRRC4C/ NGL-1 has been found to interact with netrin-G1 but not with netrin-G2. In addition, LRRC4/NGL-2 interacts with netrin-G2 but not with netrin-G1 [
9]. LRRC4B/NGL-3 does not interact with either netrin-G1 or netrin-G2 but was determined to interact with the receptor tyrosine phosphatase LAR [
10,
18]. The interaction between netrin-G1 and LRRC4C/NGL-1 has been implicated in the regulation of axonal outgrowth and migration [
8]. The LRRC4C/NGL1-netrinG1 and LRRC4/NGL2-netrinG2 interactions have been implicated in the lamina-specific segmentation of dendrites [
15]. In the early development of the brain, the expression of mLRRC4/NGL-2 increased with age, suggesting a possible role of LRRC4/NGL-2 in brain development [
13]. LRRC4/NGL-2 regulates the formation of excitatory synapses through the recruitment of pre- and postsynaptic proteins [
19], participates in the differentiation of neuron and glia cells, and promotes neurite outgrowth [
20]. In addition,LRRC4/NGL-2 formed a complex with the NMDA receptor subunits involved in the regulation of NMDA(N-methyl-D-aspartate) receptor-mediated excitatory synaptic transmission [
9]. LRRC4/NGL-2 is localized to the dendritic segment in the stratum radiatum of CA1(Cornu Ammonis 1 area) and functions as a key regulator of input-specific synapse development, which is critical for the functional integration of distinct inputs [
21]. LRRC4/NGL-2 was found to localize selectively to the tips of HC(horizontal cell) axons, which form reciprocal connections with rods; moreover, LRRC4/NGL-2 works as a central component of pathway-specific development in the outer retina [
22]. LRRC4B/NGL-3–LAR interaction is capable of mediating cell aggregation [
23]. LRRC4B/NGL-3 might be involved in the maturation of excitatory synapses. A suggested function of the LRRC4B/NGL-3–LAR interaction is synapse formation [
23]. The results from studies on the LRRC4 family suggest that LRRC4s play important roles in maintaining normal function in the central nervous system. In addition to the functions in neuronal cell types, LRRC4/NGL proteins play a role in glial cells [
10].