thereby regulating neuronal structure. This can occur within a lipid raft so as to compartmentalize and localize motility of filopodia in growth cones in developing brains, and could also remodel presynaptic terminals in adults in an activity-dependent manner. GAP-43 is also a protein kinase C (PKC) substrate. Phosphorylation of serine-41 on GAP-43 by PKC regulates neurite formation, regeneration, and synaptic plasticity. Because of the association and potential binding of GAP43 with a number of different molecules, including PKC, PIP2, actin, calmodulin, spectrin, palmitate, synaptophysin, amyloid and tau protein, it may be useful to think of GAP43 as an adaptor protein situated within the terminal in a supramolecular complex regulating presynaptic terminal functions, particularly bidirectional communication with the postsynaptic process. Its important role in memory and information storage is executed through its cell biological mechanisms of phosphorylation, palmitoylation, protein-protein interaction and structural remodeling via actin polymerization. Clinical significance Humans with a deletion in one allele of the GAP43 gene fail to form telencephalic commissures and are intellectually disabled. Model organisms Model organisms have been used in the study of GAP43 function. A conditional knockout mouse line, called Gap43tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant mice survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and increased IgG1 levels were observed in these animals. Studies on another homozygous GAP43 knockout mouse line found it to be lethal days after birth because it plays a critical role in the development of the mammalian CNS. Telencephalic commissures fail to form, thalamocortical afferents are mistargeted, especially in somatosensory, particularly barrel, cortex. GAP43 is not only important for axon targeting during development but it has been shown to be important also for the maintenance of the structure and dynamics of axonal fibres and of their synaptic terminals in wild-type rodents both during normal conditions and during lesion-induced axonal sprouting. The cerebellum is also affected. GAP43 is also haploinsufficient for the cortical phenotypes and the severity of the axon targeting phenotype is directly related to the extent to which the affected axons are phosphorylated by PKC, suggesting that axons require