Studies in MDA-MB-231 breast carcinoma cells by Bourguignon and colleagues [57] connect Rho, caveolin-1, and cathepsin B. Rho kinase signaling events, mediated upstream by CD44-NHE1 interactions localized to lipid microdomains containing caveolin-1, result in acidification of the microenvironment surrounding breast cancer cells, activate secretion of cathepsin B and promote cellular invasiveness. Here, CTSB is linked to breast carcinoma.