Lrp1, also known as low-density lipoprotein receptor-related protein 1, is an endocytic/signaling cell-surface receptor. It regulates diverse cellular functions such as cell survival, differentiation, and proliferation. It is involved in multiple pathways and is of great biological importance in maintaining homeostasis in various tissues [1,2]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in studying its functions.

In the context of disease, Lrp1-related KO mouse models have revealed significant insights. In a neuronal Lrp1 conditional knockout (Lrp1-nKO) mouse model, the spread of α-synuclein was significantly reduced, indicating Lrp1 as a key regulator of α-synuclein neuronal uptake and spread, relevant to Parkinson's disease and Lewy body dementia [3]. Heterozygous Lrp1 knockout (Lrp1+/-) mice showed phenotypes recapitulating human developmental dysplasia of the hip (DDH), suggesting Lrp1 loss of function causes DDH [4]. Also, in mice with hepatocyte-specific Lrp1 deletion, minimal Rift Valley fever virus (RVFV) replication occurred in the liver, showing Lrp1 is essential for RVF hepatic disease in mice [5].

In conclusion, Lrp1 plays essential roles in multiple biological processes. Model-based research, especially using Lrp1 KO/CKO mouse models, has significantly contributed to understanding its functions in diseases such as neurodegenerative disorders, DDH, and viral-induced hepatic diseases. These findings provide a basis for further exploring Lrp1-targeted therapeutic strategies.