SYK (spleen tyrosine kinase) is a non-receptor tyrosine kinase that serves as a central mediator of immune receptor signaling and diverse cellular processes 1. SYK functions primarily downstream of immunoreceptors containing ITAM (immunoreceptor tyrosine-based activation motif) domains, where it initiates signaling cascades critical for adaptive and innate immunity 1. In B-cell receptor signaling, SYK phosphorylates key downstream effectors and is essential for B-cell maturation, while in T-cell contexts, aberrant ZAP70 co-expression with SYK can redirect signaling from NFAT toward PI3K pathways, promoting cell survival in malignancies 2. Beyond immune functions, SYK mediates platelet activation, osteoclast maturation, and vascular development 1. In neuroinflammation, SYK drives microglial responses to amyloid-β plaques through TREM2-dependent pathways, with SYK deficiency impairing plaque encasement and accelerating pathology 3. Therapeutically, SYK represents an attractive target, with inhibitors showing promise in treating autoimmune diseases, hematological malignancies, and potentially neurodegenerative conditions 45. Interestingly, SYK can negatively regulate some ITAM-mediated responses, as its deletion in NK cells enhances activation and cytotoxicity 6.