Insulin-induced gene 2 (INSIG2) functions as a blocker of cholesterol biosynthesis and has been shown to be involved in colon and pancreatic cancer pathogenesis. Cholesterol is a risk factor for breast cancer pathophysiology; however, the underlying mechanisms are not well defined. Hence, our goal was to determine the role of INISG2 in breast cancer. INSIG2 mRNA and protein expression was correlated to metastatic potential of breast cancer cell lines. Knockdown of INSIG2 inhibited epithelial to mesenchymal (EMT) transition. Conversely, overexpression of INSIG2 induced EMT. Knockdown of INSIG2 did not affect cell proliferation but resulted in altered metabolism in vitro and attenuated experimental metastasis in vivo. Analysis of breast cancer tissue microarrays revealed significantly higher INSIG2 protein expression in breast cancer tissues. INSIG2 protein expression was correlated to hormone receptor status with significantly higher expression in patients with triple negative (TNBC) and HER2- molecular subtypes of invasive breast cancer. Analysis of The Cancer Genome Atlas (TCGA) however revealed significantly lower INSIG2 mRNA expression in TNBC patients. Higher INSIG2 mRNA expression was correlated to poor survival probability. Asian patients with high INSIG2 mRNA expression had significantly lower survival probability compared to Asian patients with low/medium INSIG2 mRNA expression. These results reveal a yet undefined role of INSIG2 in breast cancer, potentially more relevant for breast cancer patients in Asia.Copyright © 2020. Published by Elsevier Inc.