7-dehydrocholesterol reductase (DHCR7)

7-dehydrocholesterol reductase (DHCR7) is an essential membrane-bound enzyme in the endoplasmic reticulum that catalyzes the final reduction step of 7-dehydrocholesterol to cholesterol, using NADPH as a cofactor[1][3][5]. This step is crucial not only for cholesterol biosynthesis, fundamental for cellular structure, signaling, and hormone production, but also indirectly influences vitamin D synthesis by regulating the availability of its precursor in skin[3][4][5]. DHCR7 activity is tightly regulated by cholesterol feedback, phosphorylation, and other mechanisms[6]. Deficiency or inhibition of DHCR7 leads to the accumulation of 7-DHC, reduced cholesterol, and the pathogenesis of Smith-Lemli-Opitz syndrome, a developmental disorder presenting with congenital malformations and neurodevelopmental impairment[1][3][4][5]. DHCR7 is also implicated in immune response modulation[3], and disturbances in its function can be detrimental to embryonic viability and health. Therapeutic targeting involves both direct enzyme inhibition (investigational) and biomarker-guided diagnosis, such as monitoring 7-DHC and cholesterol levels[3][5].

Other names

DHCR7D7SR7-DHC reductaseDelta7-sterol reductaseSterol Delta(7)-reductaseSterol reductase SR-2Cholesterol-5,6-epoxide hydrolase subunit DHCR7SLOS genedelta-7-dehydrocholesterol reductase

Enzyme inhibition (drugs inhibit DHCR7 activity, causing decreased cholesterol production and increased 7-DHC levels; this mechanism underlies developmental toxicity in animal models)