Bruton tyrosine kinase (BTK)

Bruton agammaglobulinemia tyrosine kinase (BTK) is a non-receptor tyrosine kinase that plays an essential and non-redundant role in B-cell development, maturation, and signaling. It is a member of the Tec family of kinases and is encoded by the BTK gene located on the X chromosome. BTK was originally identified as the gene mutated in X-linked agammaglobulinemia (XLA), a primary immunodeficiency characterized by the near-complete absence of circulating B cells and immunoglobulins. In physiological B-cell biology, BTK functions as a pivotal component of the B-cell receptor (BCR) signaling cascade, transmitting activation signals downstream through phospholipase C gamma 2 (PLCG2) and connecting to pathways including the PI3K/Akt signaling pathway, NF-κB, and MAPK. Beyond its canonical role in lymphocytes, BTK is expressed in myeloid lineage cells including neutrophils and macrophages, where it participates in innate immune receptor signaling.

Given its central position in BCR-mediated survival and proliferation signals, BTK has emerged as one of the most validated pharmacological targets in hematological oncology. Small-molecule inhibitors of BTK — spanning covalent, irreversible agents (such as ibrutinib) and next-generation non-covalent inhibitors — have transformed the treatment landscape for B-cell malignancies, particularly chronic lymphocytic leukemia (CLL). More recently, BTK has attracted attention in inflammatory and autoimmune disorders, as well as in exploratory investigations in neurological conditions, reflecting the breadth of its signaling roles across hematopoietic and immune cell types.