A plethora of studies have identified the “autophagy-lysosome pathway”, a major cellular degradation system, as one of the important mechanisms involved in regulating the immune-mediated pathogen clearance mechanisms in several infection models [5,6,7]. Evidence suggests that a specific form of autophagy, called “xenophagy”, is responsible for the elimination of bacterial, viral or fungal pathogens [7,8,9,10]. In general, autophagy (mainly macroautophagy) is one of the two components of the cellular homeostatic machinery called the “proteostasis network (PN)” [11,12,13,14], which could be termed as the “master regulator of cellular well-being”, as it regulates all the processes involved in protein turnover in the cell. The other component of the PN is the ubiquitin-proteasome system (UPS), which deals primarily with the degradation of cellular proteins [15,16,17,18,19] which allows protein turnover and a replacement of misfolded proteins, as well as the regulation of vital regulatory proteins involved in a variety of cellular homeostatic processes. In contrast, the autophagy-lysosome pathway can handle the degradation of much broader and larger cargo, such as protein aggregates, lipids, damaged organelles, or infectious agents such as bacteria and viruses [9,20,21,22,23,24]. These two components of the PN play a vital role in maintaining cellular homeostasis by facilitating the removal of these dysfunctional cellular components while maintaining or replenishing the levels of proteins, lipids, etc., via synthetic machinery. Other proteostatic mechanisms include the unfolded protein response (UPR), small ubiquitin-like modifier (SUMO), and the endoplasmic reticulum (ER)-associated degradation (ERAD) pathways. Both SUMO and ERAD have a role in the trafficking of the misfolded cystic fibrosis transmembrane conductance regulator (CFTR), which is the dysfunctional protein responsible for the pathogenesis of CF [25,26]. Furthermore, the dysregulation of UPR has been shown to lead to an exaggerated inflammatory response that plays a role in CF pathogenesis progression and exacerbations [27]. Therefore, it is evident that any dysregulation of the PN components leads to severe life-threatening diseases that includes proteinopathies, neurodegenerative diseases, age-related disorders, and chronic respiratory diseases such as CF and COPD [11,13,15,28,29,30].