Background and Aims <p>Activation of hepatic stellate cells (HSCs) and subsequent dysregulation of the TGF-β1 signaling pathway are central to the progression of hepatic fibrosis. Neuropilin-1 (NRP1) has been identified as a co-receptor involved in multiple signaling pathways, yet its role in modulating TGF-β receptor stability in HSCs remains to be fully elucidated. This study investigated the regulatory role of the NRP1/Src/Rab7 axis in TβRI lysosomal degradation during HSC activation.</p> Methods <p>Hepatic fibrosis was induced in male C57BL/6 mice via intraperitoneal CCl₄ injection for four weeks. HSC-specific knockdown of <i>Nrp1</i> was achieved using an AAV8-pLrat-sh<i>Nrp1</i> vector. TβRI stability and lysosomal degradation were evaluated through cycloheximide (CHX) chase assays and chloroquine treatment. The impact on the TGF-β1/Smad signaling pathway was assessed both in vitro and in vivo.</p> Results <p><i>Nrp1</i> silencing in primary HSCs reduced TβRI protein levels and attenuated p-Smad2/3 signaling without affecting mRNA levels. Consistently, NRP1 deficiency accelerated lysosomal degradation of TβRI, accompanied by increased TβRI–LAMP1 colocalization and enhanced trafficking of TβRI into Rab7-positive late endosomes. Mechanistically, NRP1 loss diminished Src kinase activity and consequently reduced Src-dependent tyrosine phosphorylation of Rab7, leading to elevated Rab7-GTP levels and enhanced late endosomal sorting of TβRI. <i>Rab7</i> knockdown or Src reactivation partially rescued TβRI stability and restored downstream signaling. In vivo, HSC-specific <i>Nrp1</i> knockdown attenuated CCl₄-induced fibrosis and reduced TβRI levels, while Rab7 inhibition partially reversed these effects.</p> Conclusions <p>These data suggest that the NRP1/Src/Rab7 axis contributes to TβRI stability by modulating its lysosomal degradation pathway. Targeting this axis may provide a potential approach for intervening in the progression of hepatic fibrosis.</p> <p></p>