Our findings support the involvement of CAIX in determining tissue pHe, independently of hypoxia status, and add to the therapeutic rationale for pharmacologically inhibiting CAIX, which is already an emerging drug target.48 Abrogation of this pH-stat function might reduce the acidity of the tumour microenvironment and impinge on the downstream disease mechanisms governed by this pathophysiologic feature of cancer. Here, CA9 is linked to cancer.