SEZ6 (seizure-related homolog 6) is a cell surface type 1 transmembrane protein primarily expressed in the central nervous system 1. In normal neuronal development, SEZ6 plays a critical role in cell-cell recognition and neuronal membrane signaling, regulating the balance between dendrite elongation and branching to establish appropriate excitatory synaptic connectivity 1. The protein localizes to dendritic spines, dendritic shafts, and endoplasmic reticulum compartments, contributing to synapse maturation and dendritic arbor elaboration. Beyond its developmental functions, SEZ6 has emerged as a disease-relevant target in neuroendocrine malignancies. Aberrant SEZ6 expression associates with neurodevelopmental and psychiatric disorders including epilepsy, schizophrenia, and Alzheimer disease 1. SEZ6 is substantially overexpressed in small cell lung cancer (SCLC) and other high-grade neuroendocrine neoplasms, with expression regulated by ASCL1, a lineage-defining transcription factor 1. Expression patterns vary across neuroendocrine tumor types, with strong positivity in Merkel cell carcinomas and medullary thyroid carcinomas, but lower prevalence in pancreatic and gastric neuroendocrine tumors 2. Clinically, SEZ6-targeted antibody-drug conjugates (ADCs) demonstrate therapeutic promise. ABBV-011, a calicheamicin-based SEZ6-ADC, achieved a 25% objective response rate and 3.5-month median progression-free survival in heavily pretreated SCLC patients, with manageable safety profiles 3. SEZ6 represents a novel precision medicine target for neuroendocrine malignancies.