Importantly, the unique role of SDC4—a heparan sulfate proteoglycan—as a gatekeeper of CAF-driven malignancy reveals its potential cooperation with integrins such as α2β1 (47, 48), amplifying pro-invasive mechanotransduction and offering a focused therapeutic target to disrupt stromal-epithelial signaling that underpins bladder cancer progression. The gene discussed is CD44; the disease is urinary bladder cancer.