Bruton tyrosine-protein kinase (BTK)

Bruton tyrosine-protein kinase (BTK) is a cytoplasmic non-receptor tyrosine kinase belonging to the Tec family, critically involved in B cell development, maturation, and signaling.[1][2][3][6][7] BTK transmits signals from activated B cell receptors and other immune receptors, leading to downstream activation of pathways such as phospholipase C gamma 2 (PLCγ2), nuclear factor-κB (NFκB), and MAP kinase, all central to immune cell function.[1][3] Loss-of-function mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), characterized by an absence of mature B cells and immunoglobulins with recurrent infections.[1][7] Aberrant BTK activity is implicated in B-cell malignancies and autoimmune diseases, making it a validated therapeutic target. BTK inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib) are used to treat B cell malignancies, and new indications are emerging in autoimmune and inflammatory diseases.[2][6][8] Emerging data also implicate BTK and its isoforms in several non-hematologic cancers, and in the regulation of myeloid cells and microglia, with clinical trials exploring BTK inhibition in conditions such as multiple sclerosis and solid tumors.[4][6][8]

Other names

Bruton’s tyrosine kinasetyrosine-protein kinase BTKBtk

Irreversible covalent inhibition of kinase domain (e.g., ibrutinib binds Cys481) Disruption of B cell receptor signaling Impaired survival and proliferation of malignant B-cells Modulation of myeloid or microglial cell activation