Lysine acetylation in the lumen of the ER: A novel and essential function under the control of the UPR

► Resident and transiting proteins can undergo Nε-lysine acetylation in the ER lumen. ► Two (or more) acetyl-CoA:lysine acetyltransferases are found in the ER. ► A membrane transporter translocates acetyl-CoA into the ER lumen. ► Influx of acetyl-CoA into the ER controls the induction of ERAD(II). ► Defects in the ER-based acetylation machinery are linked to human diseases.