Bruton's Tyrosine Kinase—Going Beyond the B Cell

Bruton's Tyrosine Kinase (BTK) is a cytoplasmic kinase essential for B cell-mediated signalling, yet has also received recent recognition as a direct regulator of myeloid cell function. Beyond its established role in B cell malignancies, BTK influences receptor-driven activation in monocytes, macrophages, microglia, granulocytes, and other organ-specific macrophages by influencing key molecular pathways involved in phagocytosis, inflammatory-mediated signalling, and cell metabolism (e.g., NFκB, STAT3, and NLRP3). BTK inhibitors (BTKis) were initially developed and approved to treat B cell-related cancers, however, they have also demonstrated significant therapeutic/clinical efficacy in autoimmune, allergic, and immune-driven neuroinflammatory disorders, including rheumatoid arthritis, IgA nephropathy, multiple sclerosis, and chronic spontaneous urticaria. This review specifically addresses, compares, and summarises how BTK inhibition within distinct myeloid-derived cell subsets alters inflammatory-related phenotypes and functions within these cells. Together, providing cell-specific insights into BTK as a central regulator of innate immunity and myeloid cell function may help generate significant translational potential for BTKis in multiple inflammatory-mediated diseases.