Seizure-related gene 6 protein (SEZ6)

Seizure-related gene 6 protein (SEZ6) is a type I transmembrane protein primarily expressed in the central nervous system, where it plays a vital role in neuronal maturation, dendritic branching, and the maintenance of synaptic connectivity (UniProt Q53EL9). While its name stems from its initial discovery in mouse models of epilepsy, SEZ6 has gained prominence in oncology as a highly specific cell-surface marker for small cell lung cancer (SCLC) and other neuroendocrine tumors (PubMed: 31110077). In these malignancies, SEZ6 is frequently overexpressed, whereas its expression in normal adult peripheral tissues is minimal, providing a favorable therapeutic window. Current clinical development focuses on SEZ6 as a target for antibody-drug conjugates (ADCs) like ABBV-011, which utilize the protein's internalization properties to deliver potent cytotoxic agents directly into tumor cells (ClinicalTrials.gov: NCT03639181). Additionally, SEZ6 is known to be a substrate for BACE1, suggesting potential involvement in the pathophysiology of neurodegenerative conditions such as Alzheimer's disease (PubMed: 27170014).

Other names

Seizure-related 6 homologBSRP-CSeizure-related protein 6

Antibody-drug conjugate (ADC) targeting SEZ6-expressing cells to deliver a cytotoxic payload (calicheamicin), leading to DNA damage and apoptosis.