The inhibitory effects of ibrutinib and acalabrutinib on CLEC-2-mediated platelet activation are primarily mediated through specific inhibition of BTK in the SYK-LAT-BTK-PLCγ2-NF-AT pathway and a BTK-dependent positive feedback signaling involving ADP and thromboxane A2, as CLEC-2-mediated platelet activation and aggregation are also blocked by BTK mutations in platelets of XLA patients (Nicolson et al., 2021). The gene discussed is BTK; the disease is Bruton-type agammaglobulinemia.