NCAM1 (neural cell adhesion molecule 1) is a cell surface glycoprotein with multifaceted roles in neurological, immunological, and vascular biology. Primarily, NCAM1 functions as an adhesion molecule mediating cell-cell interactions essential for neural development and axon guidance 1. Beyond its classical adhesive role, NCAM1 serves as a receptor for viral pathogens; it acts as a rabies virus entry receptor that can be competitively blocked by PDIA3 to restrict viral infection 2. Mechanistically, NCAM1 promotes pathological processes through multiple signaling pathways. In cancer, Schwann cell-expressed NCAM1 drives perineural invasion by inducing cancer cell protrusions and promoting cell dispersion, with NCAM1-deficient mice showing decreased neural invasion 1. In pulmonary hypertension, NCAM1 enhances pulmonary artery smooth muscle cell proliferation and migration via ERK1/2 signaling, with elevated serum NCAM1 correlating with disease severity 3. Clinically, NCAM1 has significant diagnostic and prognostic value. It serves as a candidate biomarker for Charcot-Marie-Tooth disease, showing elevation across multiple CMT genotypes and correlating with neuropathy severity 4. Additionally, NCAM1 is recognized as a target antigen in membranous nephropathy, an autoimmune kidney disease causing nephrotic syndrome, with distinct pathological and therapeutic implications 56. NCAM1-positive extracellular vesicles are useful for isolating neuron-derived EVs in neurodegenerative disease research 78.