isoforms, but is most commonly found in the NCAM-125 isoform. Posttranslational modification NCAM exhibits glycoforms as it can be posttranslationally modified by the addition of polysialic acid (PSA) to the fifth Ig domain, which is thought to abrogate its homophilic binding properties and can lead to reduced cell adhesion important in cell migration and invasion. PSA has been shown to be critical in learning and memory. Removal of PSA from NCAM by the enzyme endoneuraminidase (EndoN) has been shown to abolish long-term potentiation (LTP) and long-term depression (LTD). Expression in normal cells The neural cell adhesion molecule NCAM1 appears on early embryonic cells and is important in the formation of cell collectives and their boundaries at sites of morphogenesis. Later in development, NCAM1 (CD56) expression is found on various differentiated tissues and is a major CAM mediating adhesion among neurons and between neurons and muscle. Function NCAM is thought to signal to induce neurite outgrowth via the fibroblast growth factor receptor (FGFR) and act upon the p59Fyn signaling pathway. In nerves, NCAM1 regulates homophilic (like-like) interactions between neurons and between neurons and muscle; it associates with fibroblast growth factor receptor (FGFR) and stimulates tyrosine kinase activity of receptor to induce neurite outgrowth. When neural crest cells stop making N-CAM and N-cadherin, and start displaying integrin receptors, cells separate and migrate. During hematopoiesis, CD56 is the prototypic marker of NK cells, also present on subset of CD4+ T cells and CD8+ T cells. In cell adhesion, CD56 contributes to cell-cell adhesion or cell-matrix adhesion during embryonic development. Pathology In anatomic pathology, pathologists make use of CD56 immunohistochemistry to recognize certain tumors. Normal cells that stain positively for CD56 include NK cells, activated T cells, the brain and cerebellum, and neuroendocrine tissues. Tumors that are CD56-positive are myeloma, myeloid leukemia, neuroendocrine tumors, Wilms' tumor, neuroblastoma, extranodal NK/T-cell lymphoma, nasal type, pancreatic acinar cell carcinoma, pheochromocytoma, paraganglioma, small cell lung carcinoma, and the Ewing's sarcoma family of tumors. Cancer A member of the NCAM superfamily, NCAM2 gene has been observed progressively downregulated in human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, NCAM2 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. Alzheimer's disease NCAM2 is found in lower levels in hippocampal synapses of Alzheimer's disease sufferers and is found to be broken