SEZ6L2 (seizure-related 6 homolog like 2) is a cell surface protein localized on chromosome 16.2 with emerging roles in neurological and oncological pathways. Primary function: SEZ6L2 may contribute to specialized endoplasmic reticulum functions in neurons and participate in synapse maturation 1. Mechanism: The protein is transcriptionally regulated by upstream transcription factor 1 (USF1) 2 and appears to modulate cell proliferation and translation dysregulation through extracellular signal-regulated kinase signaling 3. Disease relevance: SEZ6L2 variations have been investigated in autism spectrum disorders associated with 16p11.2 microdeletions, though sequence variations alone do not show enrichment in ASD patients 1. Hemizygous deletion of SEZ6L2 contributes to sex-specific striatal phenotypes in neurodevelopmental disorder models, particularly male-specific hyperactivity and impaired reward-seeking behavior 3. In autoimmune neurological disease, SEZ6L2 has been detected as a target of neural autoantibodies in patients with cerebellar ataxia 4. Clinical significance: SEZ6L2 is consistently overexpressed in multiple cancer types including breast, hepatocellular, and colon cancers, where elevated expression correlates with poor prognosis, advanced TNM stages, and lymph node metastasis 2, 5, 6. SEZ6L2 shows potential as a prognostic biomarker and immunotherapeutic target 7. Additionally, SEZ6L2 has been identified as a genetic risk factor for endometriosis through plasma proteomic analysis 8.