Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We thank Yang and Rao for their interest in our recently published article.1 This is our reply to their questions on M2 polarization in endoplasmic reticulum (ER) stressed macrophages and the role of C/EBP homologous protein (CHOP) in this process. In our article, we inferred that reduced hepatic steatosis and injury in response to ethanol in the absence of Nogo‐B may be attributable, in part, to ER stress‐mediated M2 polarization of Kupffer cells based on our collective data and the existing literature. Other studies have also reported ER stress‐mediated M2 polarization,2 including M2 polarization by chemically induced ER stress in the presence of lipopolysaccharide similar to that used by us2 along with CHOP's involvement in this process.2 The effect of ER stress on macrophage polarization may be affected by the levels of ER stress (low vs. high, or acute vs. chronic), types of macrophages, and other experimental conditions. M2 polarization induced by higher levels of ER stress was shifted toward M1 polarization by lower levels of ER stress in a previous study.2 We induced ER stress in a murine macrophage cell line by tunicamycin (TM) (2 μg/mL for 24 hours),1 which is a stronger and longer TM treatment than the one used by Rao et al. (1 μg/mL for 6 hours in bone marrow–derived macrophages).5 These differences in experimental conditions may have contributed to the different results between the two studies. In our article, we also mentioned mechanisms other than ER stress that may modulate Nogo‐B's involvement in M2 polarization and highlight the need for further investigation.1 Advances in macrophage characterization beyond simple M1 and M2 phenotypes also add complexity and leave no doubt that the role of ER stress in macrophage polarization/differentiation needs to be scrutinized.