Dysadherin (FXYD5) is a multifunctional protein involved in tumor-promoting processes, including the regulation of Na+/K+-ATPase activity, the induction of EMT, the modulation of immune responses, and the enhancement of fibronectin-mediated adhesion, which activates integrin/FAK signaling to support migration and survival.26,29,31,33 Our study reveals a previously unrecognized role of dysadherin in enabling CRC adaptation to an acidic TME. Here, PTK2 is linked to colorectal carcinoma.