What Is 24-dehydrocholesterol reductase

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Last updated: April 15, 2026

Quick Answer: 24-dehydrocholesterol reductase (DHCR24) is an enzyme encoded by the DHCR24 gene in humans, responsible for catalyzing the final step in cholesterol biosynthesis by reducing desmosterol to cholesterol. Mutations in this gene are linked to desmosterolosis, a rare autosomal recessive disorder.

Key Facts

DHCR24 gene is located on chromosome 1p32.3
The enzyme catalyzes the reduction of desmosterol to cholesterol using NADPH as a cofactor
Desmosterolosis, linked to DHCR24 mutations, has been reported in fewer than 10 cases worldwide
DHCR24 expression is upregulated by sterol regulatory element-binding proteins (SREBPs)
The enzyme has an alternate name: Seladin-1, discovered in 2000 as a protein overexpressed in adrenal cortex and downregulated in Alzheimer’s disease

Overview

24-dehydrocholesterol reductase, also known as DHCR24, is a critical enzyme in the cholesterol biosynthesis pathway. It catalyzes the reduction of the C24 double bond in desmosterol, converting it into cholesterol—the final step in the Bloch pathway of cholesterol synthesis.

This enzyme is encoded by the DHCR24 gene located on the short arm of chromosome 1 (1p32.3) and is expressed predominantly in the brain, adrenal glands, and liver. Its activity is tightly regulated by sterol levels and plays a pivotal role in maintaining cellular membrane integrity and steroid hormone production.

Gene location: The DHCR24 gene spans approximately 37 kilobases and contains nine exons, positioned at locus 1p32.3 on chromosome 1.
Enzyme function: DHCR24 reduces desmosterol to cholesterol using NADPH as a reducing cofactor, completing the cholesterol synthesis cascade.
Tissue expression: Highest expression levels are found in the adrenal cortex, liver, and developing brain, correlating with high cholesterol demand.
Regulation: Expression is upregulated by sterol regulatory element-binding protein-2 (SREBP-2) during low intracellular cholesterol conditions.
Disease link: Biallelic mutations in DHCR24 cause desmosterolosis, a rare metabolic disorder characterized by developmental delays and dysmorphic features.

How It Works

DHCR24 functions at the endoplasmic reticulum membrane and is essential for converting desmosterol into cholesterol. This enzymatic step is vital for proper embryonic development, neurodevelopment, and steroidogenesis.

Substrate: Desmosterol is the immediate precursor to cholesterol, with a double bond at the C24 position that DHCR24 specifically reduces.
Cofactor: NADPH provides the reducing equivalents required for the conversion, with each molecule of desmosterol consuming one NADPH.
Reaction type: The enzyme catalyzes a stereospecific reduction, producing cholesterol with high enzymatic efficiency (Km ≈ 15 μM).
Membrane association: DHCR24 is an integral membrane protein with multiple transmembrane domains anchoring it to the endoplasmic reticulum.
Alternate name: Also known as Seladin-1 (Selective Alzheimer’s Disease Indicator-1), due to its reduced expression in vulnerable brain regions in Alzheimer’s patients.
Antioxidant role: Seladin-1 exhibits anti-apoptotic properties and protects cells from oxidative stress, independent of its enzymatic function.

Comparison at a Glance

Below is a comparison of DHCR24 with other key enzymes in the cholesterol biosynthesis pathway:

Enzyme	Gene	Substrate	Product	Associated Disorder
24-dehydrocholesterol reductase	DHCR24	Desmosterol	Cholesterol	Desmosterolosis
Lanosterol 14α-demethylase	CYP51A1	Lanosterol	FF-MAS	None known
7-dehydrocholesterol reductase	DHCR7	7-Dehydrocholesterol	Cholesterol	Smith-Lemli-Opitz syndrome
Squalene monooxygenase	SQLE	Squalene	Squalene 2,3-epoxide	None known
HMG-CoA reductase	HMGCR	HMG-CoA	Mevalonate	Autosomal dominant hypercholesterolemia

Unlike DHCR7, which is associated with Smith-Lemli-Opitz syndrome (SLOS), DHCR24 deficiency leads to a distinct disorder with overlapping but more severe symptoms, including microcephaly, cleft palate, and limb malformations. The rarity of desmosterolosis—fewer than 10 documented cases—makes it one of the least common inborn errors of cholesterol metabolism.

Why It Matters

Understanding DHCR24 is crucial for diagnosing rare metabolic disorders and exploring neurodegenerative disease mechanisms. Its dual role in cholesterol synthesis and cellular protection underscores its biological significance.

Diagnostic marker: Elevated desmosterol levels in plasma and tissues are a biochemical hallmark of DHCR24 deficiency.
Therapeutic target: Inhibiting DHCR24 may have implications in cancer, as Seladin-1 is overexpressed in some carcinomas.
Neuroprotection: The anti-apoptotic function of Seladin-1 suggests potential roles in preventing neuronal death in Alzheimer’s disease.
Drug interactions: Some antifungal azoles inhibit DHCR24, leading to off-target effects on cholesterol synthesis.
Developmental impact: Cholesterol is essential for Hedgehog signaling, and DHCR24 mutations disrupt embryonic patterning.
Evolutionary conservation: DHCR24 is highly conserved across vertebrates, indicating fundamental physiological importance.

Research into DHCR24 continues to reveal its multifaceted roles in health and disease, making it a key focus in lipid metabolism and neurobiology.