Mice deficient in CH25H, an enzyme crucial for the metabolism of cholesterol toward the oxysterol 7α,25‐OHC, or EBI2, the main receptor of 7α,25‐OHC, did not generate iBALT in their lungs following exposure to chronic CS and were protected against the development of COPD. Here, CH25H is linked to chronic obstructive pulmonary disease.