To identify transcriptomic changes following CRISPLD2 suppression in primary lung fibroblasts, we performed RNA‐seq expression profiling of primary HLFs from four healthy (age: 65–77 years, male) and four COPD human patients (age: 58–68 years, male, moderate‐severe COPD, GOLD classification) transfected with siRNA negative control (HLF NCsiRNA) or CRISPLD2 knockdown (HLF CRISPLD2siRNA), in technical duplicates. Here, CRISPLD2 is linked to chronic obstructive pulmonary disease.