Our data indicate the involvement of LGR6 in CLDs, suggesting a pro-regenerative LGR6-mediated activation of canonical Wnt/β-catenin pathway in COPD and IPF, which ultimately results in a chronic signalling that fosters the acquisition of a senescent phenotype and the exhaustion of lung epithelial progenitors. Here, LGR6 is linked to idiopathic pulmonary fibrosis.