Cholesterol sulfate: pathophysiological implications and potential therapeutics

Cholesterol sulfate (CS) is a naturally occurring cholesterol derivative that is widely distributed in a variety of tissues and body fluids. In humans, CS is mediated primarily by the sulfotransferase (SULT) 2B1b (SULT2B1b). Over the years, CS has been revealed to be involved in various physiological processes, such as epidermal cell adhesion, sperm capacitation, platelet adhesion, coagulation, glucolipid metabolism, bone metabolism, gut microbiota metabolism, neurosteroid biosynthesis, T-cell receptor signaling, and immune cell migration. In this review, we first introduce the endogenous regulation of CS biosynthesis and metabolism and then highlight current advances in the understanding of the physiological roles of CS. Finally, we focused on the implications of CS in various diseases, predominantly considering its mechanism of action, and potential therapeutic application.