Lrp8, also known as low-density lipoprotein receptor-related protein 8 or apolipoprotein E receptor 2 (ApoER2), is a cell membrane receptor in the LDL receptor family. It plays a crucial role in selenium transport, as it binds to selenoprotein P (SELENOP) to deliver selenium, an essential trace element, especially to the brain at the blood-brain barrier [2]. This process is vital for several important brain functions.

Genetic deletion of Lrp8 leads to ferroptosis in MYCN-amplified neuroblastoma cells due to insufficient selenocysteine supply for the translation of antiferroptotic selenoprotein GPX4, uncovering a potential therapeutic strategy for high-risk neuroblastoma [1]. In Lrp8 knockout orthotopic xenografts, this vulnerability was further confirmed. Lrp8-knockout mice fed a selenium-replete diet showed subtle deficits in spatial learning and memory function, indicating its importance in maintaining normal brain cognitive function [2].

In summary, Lrp8 is essential for selenium-related biological functions, especially in the brain. The use of gene knockout models, such as in neuroblastoma xenografts and knockout mice, has revealed its role in protecting cancer cells from ferroptosis and in normal brain function, offering potential therapeutic targets for high-risk neuroblastoma and insights into brain-related disorders.