Ccr5, a cell membrane protein from the G protein-coupled receptors (GPCR) family, is a crucial modulator for leukocyte activation and mobilization. It is best known as an important coreceptor used by HIV to infect target cells [1,5,6,8]. Additionally, it is involved in the chemokine system, which mediates acute inflammation by guiding leukocyte migration to damaged or infected tissues [8].

Genetic deficiency of Ccr5 confers a significant degree of protection against HIV infection, and since this deficiency does not seem to cause adverse health effects, targeting Ccr5 is a promising strategy for HIV treatment and prevention [1]. In metastatic colorectal cancer, the CCR/L5 axis (including Ccr5) has dichotomous functions in cancer, influencing both tumor progression and immune responses. Low expression of this axis was correlated with improved survival, especially in patients treated with chemotherapy plus cetuximab [2]. Ccr5 promotes immune responses by recruiting immune cells to the sites of inflammation/tumor, and also contributes to an immune-suppressive tumor microenvironment, thus recognized as a potential therapeutic target for cancer [3]. In paclitaxel-induced peripheral neuropathy, blockade of Ccr5 suppresses the development of neuropathic nociception, suggesting it as a target for treatment [4]. In pulmonary ischemia-reperfusion injury, Ccr5 drives NK cell-associated airway damage, and its blockade could be a preventative treatment [7].

In summary, Ccr5 is essential in multiple biological processes and disease conditions. Its role in facilitating HIV infection, affecting cancer progression, contributing to peripheral neuropathy, and driving airway damage in pulmonary ischemia-reperfusion injury has been revealed through various studies. Understanding Ccr5 through genetic models like knockout or conditional knockout mouse models can provide valuable insights into these disease mechanisms, potentially leading to new therapeutic strategies for these diseases.