We now dissect the relative contributions of PI3K and mTOR signaling to TGF-β1-induced collagen deposition and report that rapamycin-insensitive mTORC1/4E-BP1 signaling is critical for this response in control and IPF-derived fibroblasts, whereas upstream canonical PI3K/Akt signaling is dispensable. Here, AKT1 is linked to idiopathic pulmonary fibrosis.