Sez6l2, or Seizure Related 6 Homolog Like 2, is a type 1 transmembrane protein highly expressed in the brain, especially in the hippocampus and cerebellar cortex [7]. It has implications in neuronal and motor function development and may be involved in regulating cell fate [3]. It binds to adducin (ADD) and glutamate receptor 1 (GluR1), acting as a scaffolding protein to link GluR1 to ADD and modulating AMPA-ADD signal transduction [7].

In oncology, Sez6l2 is overexpressed in several tumor entities. In breast cancer, it is transcriptionally regulated by USF1 and accelerates cell growth and metastasis [2]. In colorectal cancer, its knockdown promotes caspase-dependent apoptosis, impairing tumor growth [3]. In thyroid carcinoma, high expression of Sez6l2 is an independent prognostic indicator related to clinical progression [4]. In cholangiocarcinoma, it can serve as a biomarker to predict prognosis and is related to angiogenesis through growth factors and the P38-MAPK pathway [6]. In colon cancer, it promotes cell viability, and bexarotene can downregulate its expression, reducing cell viability [8]. Also, Sez6l2 has been associated with autoimmune cerebellar syndromes. For example, in paraneoplastic cerebellar syndrome, serum anti-Sez6l2 antibodies can be increased, and neurological symptoms may improve after tumor therapy [1]. Intense sequential immunotherapy may improve the condition of some patients with Sez6l2 antibody-associated cerebellar ataxia [5].

In conclusion, Sez6l2 is crucial for neuronal and motor function development. In disease, its overexpression in various cancers often predicts a poor prognosis, making it a potential biomarker and therapeutic target. Its association with autoimmune cerebellar syndromes also highlights its significance in neurological disorders. Research on Sez6l2 provides insights into disease mechanisms and may lead to new treatment strategies.