Collapsin response mediator protein-2 (DPYSL2 or CRMP2) is a multifunctional 
adaptor protein within the central nervous system. In the developing brain or 
cell cultures, CRMP2 performs structural and regulatory functions related to 
cytoskeletal dynamics, vesicle trafficking and synaptic physiology whereas CRMP2 
functions in adult brain are still being elucidated. CRMP2 has been associated 
with several neuropathologic or psychiatric conditions including Alzheimer's 
disease (AD) and schizophrenia, either at the level of genetic polymorphisms; 
protein expression; post-translational modifications; or protein/protein 
interactions. In AD, CRMP2 is phosphorylated by glycogen synthase kinase-3β 
(GSK3β) and cyclin dependent protein kinase-5 (CDK5), the same kinases that act 
on tau protein in generating neurofibrillary tangles (NFTs). Phosphorylated 
CRMP2 collects in NFTs in association with the synaptic structure-regulating 
SRA1/WAVE1 (specifically Rac1-associated protein-1/WASP family 
verprolin-homologous protein-1) complex. This phenomenon could plausibly 
contribute to deficits in neural and synaptic structure that have been well 
documented in AD. This review discusses the essential biology of CRMP2 in the 
context of nascent data implicating CRMP2 perturbations as either a correlate 
of, or plausible contributor to, diverse neuropathologies. A discussion is made 
of recent findings that the atypical antidepressant tianeptine increases CRMP2 
expression, whereas other, neuroactive small molecules including the epilepsy 
drug lacosamide and the natural brain metabolite lanthionine ketimine appear to 
bind CRMP2 directly with concomitant affects on neural structure. These findings 
constitute proofs-of-concept that pharmacological manipulation of CRMP2 is 
possible and hence, may offer new opportunities for therapy development against 
certain neurological diseases.