Lrrk1, or leucine-rich repeat kinase 1, is a member of the ROCO family of proteins in humans, homologous to Lrrk2. It has multiple essential functions and is involved in various biological pathways. Lrrk1 is associated with bone diseases, and its functions include regulating intracellular trafficking, cilia dynamics, and signaling pathways such as those related to EGFR, mitophagy, and B-cell responses [1,2,3,5]. Genetic models, especially knockout (KO) mouse models, are valuable for studying Lrrk1's functions.

In KO mouse models, Lrrk1-deficient mice show severe osteopetrosis phenotypes due to osteoclast cytoskeletal dysfunction. Lrrk1 phosphorylates L-plastin at serine 5, which may contribute to actin assembly in mature osteoclasts [4]. In B-cell-related studies, Lrrk1(-/-) mice exhibit altered B1a-cell development, basal immunoglobulin production, and defects in IgG3 class-switch recombination and B-cell proliferation and survival upon BCR stimulation, revealing its role in B-cell responses and CARMA1-dependent NF-κB activation [5].

In conclusion, Lrrk1 plays crucial roles in multiple biological processes, including those related to bone development, intracellular trafficking, and immune responses. The use of KO mouse models has significantly contributed to understanding Lrrk1's functions in bone-related diseases and B-cell-mediated immune responses. These findings provide insights into the mechanisms underlying these biological processes and potential targets for treating associated diseases.