Atypical chemokine receptor 4 (ACKR4/CCX‐CKR): A comprehensive exploration across physiological and pathological landscapes in contemporary research.

Atypical chemokine receptor 4 (ACKR4), also known as CCX‐CKR, is a member of the chemokine receptor family that lacks typical G protein signaling activity. Instead, ACKR4 functions as a scavenger receptor that can bind and internalize a wide range of chemokines, influencing their availability and activity in the body. ACKR4 is involved in various physiological processes, such as immune cell trafficking and the development of thymus, spleen, and lymph nodes. Moreover, ACKR4 has been implicated in several pathological conditions, including cancer, heart and lung diseases. In cancer, ACKR4 plays a complex role, acting as a tumor suppressor or promoter depending on the type of cancer and the stage of the disease. For instance, ACKR4 may inhibit the growth and metastasis of breast cancer, but it may also promote the progression of hepatocellular carcinoma and gastric cancer. In inflammatory situations, ACKR4 has been found to modulate the recruitment and activation of immune cells, contributing to the pathogenesis of diseases such as myocardial infraction and pulmonary sarcoidosis. The study of ACKR4 is still ongoing, and further research is needed to fully understand its role in different physiological and pathological contexts. Nonetheless, ACKR4 represents a promising target for the development of novel therapeutic strategies for various diseases. Significance Statement: The exploration of Atypical Chemokine Receptor 4 (ACKR4/CCX‐CKR) represents a pivotal and timely endeavor in contemporary research, as it delves comprehensively into both the physiological and pathological landscapes. Investigating the multifaceted roles of ACKR4 across these contexts not only enhances our understanding of its fundamental biological functions but also sheds light on its potential implications in various diseases. This research contributes significantly to the current knowledge in cell biochemistry and function, offering insights that could pave the way for novel therapeutic interventions and diagnostic strategies. The comprehensive examination of ACKR4 aligns with the evolving landscape of molecular and cellular research, positioning it as a crucial player in unraveling the intricacies of cellular signaling and function, thereby advancing the frontiers of scientific knowledge in the field. [ABSTRACT FROM AUTHOR]