The cover image is a photomicrograph (200X magnification) of mouse skin stained with antibody to activating transcription factor 6 alpha (ATF6α; red). Nuclei were counterstained with 4′,6-diamidino-2-phenylindole (DAPI; blue). The color images were taken separately using an Olympus BX 51 Fluorescent microscope and then merged. When unfolded protein response (UPR) is activated, ATF6α translocates from endoplasmic reticulum (ER) membrane to the Golgi apparatus, where it undergoes cleavage by site-1 protease (S1P) and S2P. Cleaved ATF6α migrates to the nucleus (violet, reflecting its overlay with DAPI blue staining) and induces transcription of UPR target genes. New work reported in this issue of the journal found that sub-chronic arsenic exposure activated reactive oxygen species (ROS)- dependent UPR signaling pathways (including the ATF6α pathway), which enhanced inflammation in murine skin. UPR signaling is under intensive investigation in inflammatory diseases and cancers. See article by Li et al. (beginning on page 2101) for more information.