This review discusses the chemokine receptor CCR5 and its role in HIV-1 infection. Chemokines are cytokines that regulate various biological processes and immune responses by interacting with G protein-coupled cell surface receptors (GPCRs). CCR5, a member of the GPCR family, plays a crucial role in HIV-1 infection by acting as a co-receptor alongside CD4. The review highlights the structural variability of CCR5, which can be influenced by post-translational modifications, G-protein coupling, conformational changes, surface density, oligomerization, and lipid environment. This variability allows HIV-1 to exploit different conformations of CCR5 to infect host cells, making it challenging to develop effective antiretroviral therapies. The review also discusses therapeutic strategies targeting CCR5, including the development of CCR5 ligands, antibodies, and genome editing techniques. The CCR5 delta-32 mutation, which confers resistance to HIV-1 infection in some individuals, is also explored. The conclusion emphasizes the complexity of CCR5's structural variability and its implications for HIV-1 infection, highlighting the need for further research to develop more effective treatments.This review discusses the chemokine receptor CCR5 and its role in HIV-1 infection. Chemokines are cytokines that regulate various biological processes and immune responses by interacting with G protein-coupled cell surface receptors (GPCRs). CCR5, a member of the GPCR family, plays a crucial role in HIV-1 infection by acting as a co-receptor alongside CD4. The review highlights the structural variability of CCR5, which can be influenced by post-translational modifications, G-protein coupling, conformational changes, surface density, oligomerization, and lipid environment. This variability allows HIV-1 to exploit different conformations of CCR5 to infect host cells, making it challenging to develop effective antiretroviral therapies. The review also discusses therapeutic strategies targeting CCR5, including the development of CCR5 ligands, antibodies, and genome editing techniques. The CCR5 delta-32 mutation, which confers resistance to HIV-1 infection in some individuals, is also explored. The conclusion emphasizes the complexity of CCR5's structural variability and its implications for HIV-1 infection, highlighting the need for further research to develop more effective treatments.