TG2 is a multifunctional enzyme involved in a variety of cellular processes such as cell death, autophagy and inflammation. The TG2 activity leads to the sequestration of proteins in aggresomes followed by their clearance by autophagy. Autophagy is a cytoprotective mechanism for the degradation of misfolded proteins and damaged organelles. It has been demonstrated that CF is characterized by defective autophagy and impaired clearance of aggresomes, favouring the accumulation of misfolded proteins, such as the mutated CFTR. Therefore, the researchers intend to explore the molecular mechanisms by which TG2 regulates CFTR trafficking and how this is related to the modulation of autophagic process in CF. To this purpose, they have generated an ad hoc mouse model of CF also lacking TG2. This study might provide a platform to define novel approaches for the treatment of CF patients by identifying protective agents that are able to modulate TG2 activity as well as strategies to restore the autophagic process.