C5ar1, also known as complement 5a receptor 1, is a key receptor in the complement system. It binds to complement component C5a, a pro-inflammatory anaphylatoxin, and is involved in various inflammatory and immune-related pathways. The C5a-C5aR1 axis plays a crucial role in multiple biological processes, including the regulation of immune cell functions, inflammation, and tissue repair, and is associated with many diseases [3].

In various disease models, C5ar1 has been shown to have significant impacts. In a NASH mouse model, C5aR1 deletion reduced inflammation and fibrosis, with transcriptional profiling revealing enrichment of pathways like Toll-like receptor signaling [1]. In lupus nephritis mouse models, knocking down C5aR1 suppressed the C5a-C5aR1 axis-controlled phosphorylation of Drp1S616 and mitochondrial fission in podocytes, alleviating podocyte injury [2]. In a COVID-19 mouse model, genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology, indicating its role in COVID-19 pathophysiology [4].

In conclusion, C5ar1 is a vital receptor in the complement system, with its activation driving inflammation and tissue damage in multiple disease conditions. Studies using gene-knockout or pharmacological inhibition in mouse models have clearly demonstrated its role in diseases such as NASH, lupus nephritis, and COVID-19, suggesting that targeting C5aR1 could be a potential therapeutic strategy for these diseases.