These findings position the miR-181a-5p/OSBPL3 axis as a critical modulator of Ras pathway activation, wherein OSBPL3 ablation disrupts oncogenic signaling to restore tamoxifen sensitivity. miR-181a-5p/OSBPL3/Ras signaling axis governs tamoxifen responsiveness in hormone receptor-positive BC. The gene discussed is OSBPL3; the disease is breast cancer.