BLK is a non-receptor Src family tyrosine kinase essential for B-lymphocyte development and signaling. It phosphorylates key B-cell receptor (BCR) signaling components including CD79A and CD79B, facilitating antigen-induced B-cell activation and the pro-B to pre-B transition 1. BLK cooperates with FYN and LYN in pre-BCR-mediated NF-κB activation and contributes to BTK activation, supporting critical early B-cell developmental checkpoints. Beyond immune function, BLK regulates pancreatic beta-cell insulin secretion through PDX1 and NKX6-1 upregulation 2. BLK also phosphorylates cGAS at tyrosine 215, promoting its cytosolic retention and limiting DNA repair capacity 3. Clinically, BLK polymorphisms are strongly associated with systemic lupus erythematosus (SLE) across multiple ethnic populations, with rs13277113 A and rs2736340 T alleles conferring increased disease susceptibility 4. BLK variants also associate with primary Sjögren's syndrome 5, Kawasaki disease 6, and allergic rhinitis 7, highlighting its role in autoimmune and inflammatory pathogenesis. Gene-gene interactions between BLK and BANK1 further modulate SLE risk 8. These associations underscore BLK's importance in both normal immune homeostasis and disease pathogenesis, with potential therapeutic implications for autoimmune conditions.