STARD5 belongs to the START protein superfamily of lipid transport proteins and functions in intracellular non‐vesicular cholesterol transport. The kidney is a major site of expression and we reported STARD5 expression to be localized to the renal proximal tubules and increased in diabetic mouse kidney. The goal for this study was to characterize the HKC‐8 human proximal tubule kidney cells for STARD5 regulation by high glucose, endoplasmic reticulum (ER) stress, and oxysterols. Cells were treated with low (5 mM) or high (25 mM) glucose for 24 hr – 7 days and mRNA levels were measured by RT‐qPCR. STARD5 expression was decreased 50% under high glucose conditions, consistent with a decrease in ER stress as measured by decreased GRP78 mRNA levels. Oxysterols, ligands for the LXR nuclear receptor, had no effect on STARD5 expression but induced ABCA1 promoter activity and mRNA levels. Thus, HKC‐8 cells have an intact LXR response and express ABCA1. Tunicamycin‐induced ER stress increased STARD5 expression and enhanced cholesterol efflux from the cells but had no effect on ABCA1 mRNA levels. Our results suggest that high glucose conditions do not directly stimulate STARD5 expression or ER stress in HKC‐8 cells. Induction of ER stress, on the other hand, enhances cholesterol efflux, as well as STARD5 expression. A direct role for STARD5 in cholesterol efflux is currently under investigation.