As BTK directly interacts with TLRs and may inhibit TLR-induced cytokine production, as suggested by Marron et al. 39, this might be one important explanation for our observations (Fig. 3), which would indicate that the increase in XBP1 transcripts in XLA patients is independent of classical ER-stress response. Here, BTK is linked to Bruton-type agammaglobulinemia.