CRK encodes an adaptor protein that regulates cell adhesion, spreading, and migration through its SH2 and SH3 domains 1. The protein contains one SH2 domain and two SH3 domains that mediate selective protein-protein interactions, with the SH2 domain preferring pY-x-x-P motifs and the SH3 domain recognizing P-x-x-P-x-K sequences 2. CRK functions as a critical signal transduction mediator by facilitating the formation of multi-protein complexes upon extracellular stimuli, including growth and differentiation factors 2. The protein activates downstream effectors including guanine nucleotide exchange factors like C3G, protein kinases, and small GTPases such as Rap1 and Rac, ultimately regulating cell motility and cytoskeletal organization 2. In disease contexts, CRK and its family member CrkL are overexpressed in many human cancers and correlate with poor prognosis 3. These proteins enhance tumor cell functions including proliferation, migration, invasion, and metastasis, making them potential therapeutic targets 3. The p130Cas-Crk/CrkL axis specifically promotes tumor cell migration and invasion, representing a promising avenue for cancer drug development 4. CRK also plays important roles in immune cell functions and mechanosignaling pathways 56.