Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase and founding member of the Tec family, which also includes ITK, TEC, BMX, and TXK. BTK is activated downstream of the B-cell receptor (BCR) through a two-step mechanism: first, LYN-mediated phosphorylation of the PH domain recruits BTK to the plasma membrane, where PI3K-generated PIP3 promotes autophosphorylation at Y551 in the activation loop by SYK, followed by autophosphorylation at Y223 in the SH3 domain. Key substrates include PLCγ2, which drives calcium mobilization, PKCβ, and NF-κB pathway effectors. BTK is indispensable for BCR signaling, B-cell development, differentiation, and survival. Dysregulation drives B-cell malignancies including CLL, MCL, DLBCL, and Waldenström macroglobulinemia, as well as autoimmune diseases such as rheumatoid arthritis and lupus. Loss-of-function mutations cause X-linked agammaglobulinemia (XLA). BTK's central role in oncogenic BCR signaling, its druggable ATP-binding pocket featuring a unique cysteine (C481), and its restricted hematopoietic expression make it a premier oncology and immunology drug target.