The translation elongation factor elF5A is important for the translation of proteins with consecutive prolines, or a combination of prolines, glycines and charged amino acids, and its overexpression has been linked to cancers and increased metastasis. Interestingly, elF5A is the only protein known to be modified by hypusination, which is required for its activity. Paula Alepuz and co-workers have previously identified extracellular matrix (ECM) proteins as potential targets of elF5A, and in this study (Barba-Aliaga et al., 2021) they now investigate its role in the translation of collagen type I. The authors show here that elF5A is required for the translation of a collagen fragment when ectopically expressed in yeast. Depletion of active elF5A in mouse fibroblast cells, the prototypical producers of collagen, results in a reduction in the protein levels of collagen type I α1 chain (Col1a1), which accumulates in the perinuclear region, as well the induction of ER stress. This suggests that in the absence of active elF5A, partially synthesised Col1a1 is retained in the ER. Furthermore, abolishing elF5A hypusination in human hepatic stellate cells (HSCs) treated with the profibrotic cytokine TGF-β1 also leads to reduced Col1a1 levels, and, importantly, inhibits HSC transdifferentiation and fibrogenesis. The findings presented here thus provide important new insights into collagen synthesis and point to elF5A as a potential therapeutic target for fibrotic diseases.