Lrp10, or Low-density lipoprotein receptor-related protein 10, encodes a conserved cell surface protein. Its functions span multiple biological processes. In the immune system, it is involved in regulating CD8 T-cell fate, and in the nervous system, it may be linked to neurodegenerative diseases [1-3].

In genetic studies, loss-of-function mutations in Lrp10 in mice lead to the accumulation of naive and central memory CD8 T cells in peripheral lymphoid organs. Lrp10 post-translationally suppresses IL7 receptor (IL7R) levels. Thus, its deletion enhances T-cell homeostatic expansion via IL7R signaling, and Lrp10-deficient mice show resistance to syngeneic tumors due to dense CD8 T-cell tumor infiltration [1]. In human neurodegenerative diseases, loss-of-function variants in Lrp10 have been associated with Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). In the human brain, Lrp10 is mainly expressed in astrocytes and neurovasculature, and it interacts with SORL1 in the intracellular vesicle trafficking pathway. In patients with PD and DLB, Lrp10 is detected in Lewy bodies, and patient-derived astrocytes carrying a Lrp10 variant secrete aberrant high-molecular-weight species of Lrp10 [2,3].

In conclusion, Lrp10 plays a crucial role in regulating CD8 T-cell homeostasis in the immune system, and its dysregulation may contribute to anti-tumor immunity. In the nervous system, Lrp10 is likely involved in neurodegenerative diseases such as PD and DLB, potentially through its role in vesicle trafficking and interaction with proteins like α-synuclein. Studies using gene knockout models in mice have been instrumental in uncovering its functions in these biological processes and disease conditions.

References:

1. Russell, Jamie, Chen, Luming, Liu, Aijie, Beutler, Bruce, Nair-Gill, Evan. 2024. Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity. In EMBO reports, 25, 3601-3626. doi:10.1038/s44319-024-00191-w. https://pubmed.ncbi.nlm.nih.gov/38956225/

2. Grochowska, Martyna M, Carreras Mascaro, Ana, Boumeester, Valerie, Bonifati, Vincenzo, Mandemakers, Wim. 2021. LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies. In Acta neuropathologica, 142, 117-137. doi:10.1007/s00401-021-02313-3. https://pubmed.ncbi.nlm.nih.gov/33913039/

3. Carreras Mascaro, Ana, Grochowska, Martyna M, Boumeester, Valerie, Bonifati, Vincenzo, Mandemakers, Wim. 2024. LRP10 and α-synuclein transmission in Lewy body diseases. In Cellular and molecular life sciences : CMLS, 81, 75. doi:10.1007/s00018-024-05135-0. https://pubmed.ncbi.nlm.nih.gov/38315424/