CHL1 (cell adhesion molecule L1 like) is a transmembrane neural cell adhesion molecule belonging to the immunoglobulin superfamily that functions primarily in nervous system development and synaptic plasticity. During brain development, CHL1 regulates neuronal migration, neurite outgrowth, and axonal membrane organization 1. In mature neurons, CHL1 accumulates in axonal membranes and regulates synapse function via clathrin-dependent pathways 1. The protein undergoes ectodomain shedding followed by γ-secretase cleavage within its transmembrane domain 2. CHL1 functions as a tumor suppressor across multiple cancer types. During primary tumor growth, CHL1 is frequently downregulated (>40% of cases) in breast, kidney, colorectal, thyroid, and pancreatic cancers, facilitating tumor initiation 3. Conversely, CHL1 overexpression induces neuronal differentiation, inhibits proliferation and anchorage-independent growth, and suppresses tumor xenograft growth in neuroblastoma through inhibition of MAPK and Akt pathways 4. CHL1 deletions cause an emerging microdeletion syndrome characterized by cognitive and language impairment, motor delays, and microcephaly 51. Additionally, CHL1 appears dysregulated in both periodontitis and Alzheimer's disease pathogenesis, suggesting shared inflammatory mechanisms 6. Aberrant CHL1 expression also associates with ovarian endometriosis development 7.