Our study reveals that Fibulin-5 silencing in NSCLC is due to the hypermethylation of its promoter through 2-HG, production of which arises from a mutation in IDH1. Throwing light on the reversible modulation by IDH1 mutation of Fibulin-5 in enhancing proliferation and migration of NSCLC cells offers a promising strategy for the treatment of metastatic LC. Here, FBLN5 is linked to laryngotracheoesophageal cleft.