Neural cell adhesion molecule (NCAM) is a membrane-bound glycoprotein expressed on the surface of neuronal and glial cells. Previous in vitro studies have demonstrated that NCAM promotes neuronal functions largely via three main interaction partners: the fibroblast growth factor receptor (FGFR), a member of Src family of tyrosine kinases, Fyn and Raf1 kinase which all activate different intracellular signaling pathways. The objective was to clarify, which signaling pathways are being disrupted in NCAM knockout mice and whether FGL peptide is able to restore observed disruptions. Therefore we compared the levels of phosphorylation of FGFR1, Src kinase Fyn, Raf1 kinase, MAP kinases, Akt kinase and calcium/calmodulin-dependent kinases II and IV (CaMKII and CaMKIV) in the hippocampus of NCAM knockout mice to their wild-type littermates. The data of our study show that mice constitutively deficient in all isoforms of NCAM have decreased basal phosphorylation levels of FGFR1 and CaMKII and CaMKIV. Furthermore, NCAM-mimetic, FGL peptide, is found to be able to restore FGFR1, CaMKII and CaMKIV phosphorylation levels and thereby mimic the interactions of NCAM at this receptor in NCAM deficient mice. Also, we found that Fyn(Tyr530), Raf1, MAP kinases and Akt kinase phosphorylation in adult animals is not affected by NCAM deficiency but interestingly, we found an over-expression of another cell adhesion molecule L1. We conclude that in NCAM deficient mice FGFR1-dependent signaling is disrupted and it can be restored by FGL peptide.