['Recent studies have shown that cigarette smoke (CS)-induced oxidative-stress impairs autophagy resulting in aggresome-formation that correlates with the severity of COPD-emphysema. Although, specific step in autophagy-pathway that is impaired is unknown. Hence, in this study we aimed to evaluate the role of master autophagy-regulator and transcription factor-EB (TFEB) in CS-induced COPD-emphysema pathogenesis.', 'We first observed that TFEB-accumulates in the peri-nuclear spaces of the COPD lung tissues of tobacco-smokers and severe-emphysema subjects. Next, Beas2b cells and C57BL/6 mice were exposed to either cigarette-smoke extract (CSE) or sub-chronic-CS (sc-CS) followed by treatment with a potent TFEB-inducer drug, Gemfibrozil (GEM) (or Fisetin as an alternate) to experimentally verify the role of TFEB in COPD. Our in vitro results indicate that GEM-mediated TFEB-induction significantly (p<0.05) decreases CSE-induced autophagy-impairment (Ub/LC3β-reporter) and resulting aggresome-formation (Ub/p62-co-expression/accumulation; immuno- blotting and staining) by controlling ROS-activity (CM-DCFDA-based ROS-assay). Intriguingly, we observed that CS induces TFEB-accumulation in the insoluble protein-fractions of Beas2b cells, which shows a partial rescue with GEM treatment. Our in vivo data further verified that CS induced autophagy-impairment (increased Ub, p62 and VCP in the insoluble protein-fractions of lung/cell lysates), inflammation (IL-6 levels in BALF and iNOS expression in lung sections) and emphysema (H&E), can be mitigated by GEM-mediated TFEB-induction (p<0.05). Moreover, we verified CS induced TFEB-accumulation in the aggresome-bodies as a mechanism for emphysema pathogenesis.', 'CS-exposure impairs autophagy in COPD-emphysema by inducing localization of master autophagy regulator, TFEB to aggresome-bodies.'] Does master autophagy regulator Transcription factor-EB ( TFEB ) regulate cigarette smoke induced autophagy-impairment and COPD-emphysema pathogenesis?