Claudin-low breast cancers (CLDNlow BrCa) are aggressive malignancies characterised by low expression of cell-cell adhesion proteins and enrichment of mesenchymal and stem-like properties. Since limited therapeutic targets are available, chemotherapy is the mainstay of treatment. Neuropilin-1 (NRP1), a cell surface co-receptor, has been implicated in multiple oncogenic processes, including angiogenesis and cell migration, and identified as a regulator of CLDN low BrCa progression. This research phenotypically characterises the impact of NRP1-inhibition on CLDNlow BrCa cells and assess their responsiveness to standard chemotherapy agents through in-vitro assays and bioinformatic analysis. NRP1 was suppressed in claudin-low cells by three approaches: CRISPR-Cas9 knockdown (KD), the anti-NRP1 antibody Vesencumab, and siRNA. NRP1 CRISPR KD models were assessed by in-vitro functional assays and related driving pathways explored by NRP1-KD RNA-seq data. Also, NRP1 KD models were tested in combination with chemotherapy drugs such as doxorubicin, docetaxel, and paclitaxel. Cell-viability assays were used to measure changes in IC₅₀ after NRP1 inhibition. NRP1 CRISPR KD models demonstrated a decrease in cancer-stem/tumour-initiating capacity, migration, and invasion, without affecting proliferation compared to control cells. RNA-seq data of NRP1-KD cells revealed differential expression of stemness- and EMT-associated genes, and 14 candidates were prioritised for subsequent molecular analysis. In 2D cultures the IC₅₀ of the three chemotherapy drugs were unaffected by either Vesencumab or CRISPR knockdown; only siRNA sequence 5 produced an increase in chemosensitivity. In the next step, we will explore EMT plasticity in NRP1-KD RNA-seq data to uncover pathways potentially linking anti-invasive phenotypes to persistent chemoresistance observed in-vitro.