TAGLN (transgelin) is an actin cross-linking/gelling protein that functions as a mechanosensitive regulator of cellular plasticity and pathological fibroblast differentiation. Mechanistically, TAGLN acts as a bridge between mechanical cues and cellular metabolism through the RhoA/ROCK2 signaling pathway 1. In this pathway, TAGLN regulates expression of the glucose carrier SLC2A3, thereby coordinating mechanotransduction with glycolytic metabolism to control fibroblast motility and secretory function 1. TAGLN also responds to environmental stiffness to promote cancer progression, forming a regulatory loop with Src activation that drives ovarian cancer dissemination through RhoA/ROCK signaling 2. In disease contexts, TAGLN marks pathogenic myofibroblasts: Fusobacterium-induced TGF-β signaling drives fibroblast-to-myofibroblast transition via TAGLN upregulation in endometriosis pathogenesis 3, and elevated TAGLN expression characterizes fibroblasts promoting skin fibrosis 1. TAGLN also supports glioblastoma stem cell survival under hypoxia by stabilizing HDAC2 to deacetylate p53 and maintain self-renewal 4. Additionally, TAGLN serves as a prognostic biomarker, with elevated expression in colorectal cancer-associated fibroblasts correlating with poor patient outcomes 5. These findings identify TAGLN as a key therapeutic target in fibrotic and neoplastic diseases.