Here, we focused on the putative regulatory role of β3-AR in H+-ATPase expression and function in mouse kidneys, considering that i) mammals basically cope with acidic dietary intake; ii) the A-ICC is the largest population of ICC (Kim et al., 1999); iii) in the kidney, β3-AR is coupled with Gs protein (Procino et al., 2016), and the cAMP-mediated translocation of the subapical pool of H+-ATPases to the apical membrane of A-ICC is a key event occurring during metabolic acidosis (Paunescu et al., 2010). The gene discussed is ADRB3; the disease is intrahepatic cholangiocarcinoma.