Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase essential for B lymphocyte development and signaling 1. Upon B-cell antigen receptor (BCR) engagement, BTK phosphorylates phospholipase C gamma 2 (PLCG2) in cooperation with adapter protein BLNK, triggering downstream calcium mobilization and protein kinase C activation 2. BTK functions as a signaling platform coordinating diverse proteins and participates in toll-like receptor (TLR) pathways, acting as a critical regulator of TLR9 activation in splenic B cells 3. Within TLR signaling, BTK induces TIRAP phosphorylation and degradation, and activates NF-κB to regulate hundreds of genes 1. BTK also phosphorylates NLRP3 to promote inflammasome assembly 4 and phosphorylates DDX41 to mediate STING1-dependent type I interferon responses 5. BTK regulates transcription factors including GTF2I, ARID3A, and NFAT, though it does not directly bind DNA 67. Clinically, BTK inhibitors have revolutionized treatment of chrX lymphocytic leukemia and other B-cell lymphomas 8, with newer noncovalent inhibitors like pirtobrutinib overcoming C481 mutation-mediated resistance 9. BTK inhibition is also being investigated for multiple sclerosis, where BTK expression in microglia and B cells contributes to CNS neuroinflammation 1011.