Fibrosis in the liver is driven by hepatic stellate cells (HSCs), which sense changes in their local environment associated with injury or chronic disease and transdifferentiate into myofibroblasts. Differentiating HSCs form more robust actin filaments, which confer increased cell contractility, migration and proliferation, and activate signalling pathways promoting collagen secretion. These responses depend on mechanosensing of forces from the extracellular matrix (ECM), which is linked to the actin cytoskeleton via structures such as focal adhesions. In this study (Hijazi et al., 2023), Nour Hijazi, Zengdun Shi and Don Rockey identify a major role for the focal adhesion-associated protein paxillin in liver fibrosis. Using in vitro and in vivo approaches, they find that overexpression of paxillin promotes fibrogenic pathways and exacerbates fibrosis in a mouse liver injury model, whereas conditional knockout of paxillin in HSCs suppresses it. Activated HSCs upregulate paxillin and increase focal adhesions, leading to greater association between paxillin and actin, increased actin polymerisation and longer actin filaments. The authors also show that paxillin regulates collagen secretion via ERK signalling downstream of actin polymerisation, suggesting that paxillin is an important node in mechanotransduction of signals that promote fibrogenic behaviours in HSCs. Thus, targeting paxillin in liver fibrosis could potentially help to ameliorate disease progression.