To identify specific kinases whose loss is synthetic lethal with chemotherapy we performed a kinase-directed shRNA screen in colorectal cancer (CRC) cells resistant to 5-Fluorouracil (5-FU) due to the loss of p53 (Grassilli et al., 2013) and, among the strongest hits, we identified a novel BTK isoform, which we dubbed p65BTK from his apparent molecular weight (Grassilli et al., 2016). Here, BTK is linked to colorectal carcinoma.