HHIPL1 is a paralog of the hedgehog signaling modulator HHIP,5 which interacts with each of the 3 hedgehog ligands and inhibits signaling.6,11,12 HHIP is associated with lung function and chronic obstructive pulmonary disease in humans,33,34 and homozygous knockout of Hhip in mice causes lethality because of abnormal lung development,35 whereas heterozygous knockout animals develop emphysema.36 The function of HHIPL1 has not been investigated previously. Here, HHIPL1 is linked to chronic obstructive pulmonary disease.