Although genome-wide association studies (GWAS) have identified the 4q31 locus7–9 nearby HHIP (hedgehog interacting protein) gene as one of the most replicated loci in COPD, including both emphysema10,11 and airway remodeling12, as well as pulmonary function in general populations2,13–15, the molecular mechanisms underlying this genetic association remain largely unknown. This evidence concerns the gene HHIP and chronic obstructive pulmonary disease.