Interestingly, a recent study has shown that Pfn2 can promote SMAD3 transcription epigenetically in lung cancer cells through suppressing the recruitment of HDAC1 to the SMAD3 promoter.14 In our case, we do not believe that loss of Pfn1 is promoting SMAD3 transcription indirectly through affecting Pfn2 activity (possibly through relieving a competition between two isoforms for a common binding factor) for two reasons. Here, PFN1 is linked to lung cancer.