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. It has implications in neuronal and motor function development, and is involved in cell fate regulation [1,6].

In oncology, Sez6l2 overexpression serves as a negative prognostic marker in several tumor entities. In breast cancer, it is transcriptionally regulated by USF1 and accelerates cell growth and metastasis [2]. In colorectal cancer, knockdown of Sez6l2 inhibits cell growth and colony formation, and promotes caspase-dependent apoptosis [3]. In thyroid carcinoma, high expression of Sez6l2 is an independent risk factor for progression-free interval [5]. In cholangiocarcinoma, it can be used to predict prognosis and is related to angiogenesis [7]. In colon cancer, it serves as a potential biomarker, and bexarotene treatment can down-regulate its expression [8]. Additionally, anti-Sez6l2 antibodies have been associated with paraneoplastic cerebellar syndrome and cerebellar ataxia [1,4].

In conclusion, Sez6l2 plays a crucial role in both neuronal development and tumor progression. Its overexpression is linked to poor prognosis in multiple cancers, and its association with autoimmune cerebellar syndromes highlights its significance in both neurological and oncological research. Understanding Sez6l2 through model-based research provides insights into disease mechanisms and potential therapeutic targets.