Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays a crucial role in various biological functions, including adaptive and innate immune responses, cellular adhesion, osteoclast maturation, platelet activation, and vascular development. SYK is activated by C-type lectins and integrins, and it activates novel targets such as the CARD9/CARMA1–BCL10–MALTI pathway and the NLRP3 inflammasome. Drosophila studies suggest that SYK-mediated signaling has an ancient evolutionary origin. SYK is essential for the development and function of immune cells, including B cells, T cells, and osteoclasts. It also regulates non-immune functions such as bone metabolism, platelet functions, and vascular development. SYK is involved in the pathogenesis of autoimmune diseases and hematological malignancies, and its inhibition has shown therapeutic potential in clinical trials. The diverse roles of SYK highlight its importance in both physiological and pathological processes, and further research is needed to fully understand its mechanisms and therapeutic applications.Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays a crucial role in various biological functions, including adaptive and innate immune responses, cellular adhesion, osteoclast maturation, platelet activation, and vascular development. SYK is activated by C-type lectins and integrins, and it activates novel targets such as the CARD9/CARMA1–BCL10–MALTI pathway and the NLRP3 inflammasome. Drosophila studies suggest that SYK-mediated signaling has an ancient evolutionary origin. SYK is essential for the development and function of immune cells, including B cells, T cells, and osteoclasts. It also regulates non-immune functions such as bone metabolism, platelet functions, and vascular development. SYK is involved in the pathogenesis of autoimmune diseases and hematological malignancies, and its inhibition has shown therapeutic potential in clinical trials. The diverse roles of SYK highlight its importance in both physiological and pathological processes, and further research is needed to fully understand its mechanisms and therapeutic applications.