<p>Leucine rich repeat containing 15 (LRRC15) is recognized for its intimate association with the extracellular matrix, where it modulates fibroblast function and shapes the immune landscape within the tumour microenvironment. The specific expression patterns and molecular contributions of LRRC15 in triple-negative breast cancer(TNBC) have not been fully elucidated. This study aimed to delineate the clinical relevance and biological implications of LRRC15 in TNBC, and to assess its potential as a novel therapeutic target for this disease. Our findings revealed robust overexpression of LRRC15 in TNBC tumour tissues and cell lines, which was inversely correlated with patient survival outcomes. Notably, the suppression of LRRC15 expression led to pronounced inhibition of TNBC cell proliferation, invasion, and migration both in vitro and in vivo. Mechanistically, we established that LRRC15 interacts with Integrin Beta 1(ITGB1), facilitating the phosphorylation of the T788/T789 residues on ITGB1 and recruiting focal adhesion kinase (FAK) to the site of integrin aggregation. This recruitment promotes the downstream phosphorylation of PI3K and AKT, suggesting that LRRC15 is a key activator of the ITGB1/FAK/PI3K signalling pathway. Collectively, our data indicate that LRRC15 is a critical promoter of TNBC cell proliferation and metastasis through the activation of this signalling pathway, identifying LRRC15 as a promising candidate for therapeutic intervention in TNBC.</p>