NSDHL Human

NAD(P) Dependent Steroid Dehydrogenase-Like (NSDHL) is an enzyme that plays a crucial role in the biosynthesis of cholesterol. This enzyme is encoded by the NSDHL gene and is localized in the endoplasmic reticulum. It is involved in the oxidative decarboxylation of the C4 methyl group from meiosis-activating sterol (MAS), which is a critical step in the cholesterol biosynthesis pathway .

Cholesterol is an essential component of cell membranes and serves as a precursor for the synthesis of steroid hormones, bile acids, and vitamin D. The proper functioning of NSDHL is vital for maintaining cholesterol homeostasis in the body. Dysregulation of cholesterol biosynthesis can lead to various diseases, including cardiovascular diseases, cancer, and metabolic disorders .

Mutations in the NSDHL gene are associated with CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects), an X-linked dominant disorder of lipid metabolism. This condition is characterized by disturbed cholesterol biosynthesis and is typically lethal in males . Additionally, NSDHL has been implicated in the progression of certain cancers, such as breast cancer. Studies have shown that high NSDHL expression is associated with reduced recurrence-free survival in breast cancer patients .

Recent research has focused on understanding the structure and function of NSDHL to develop targeted therapies. Crystal structures of human NSDHL have been determined, revealing detailed information about the coenzyme-binding site and conformational changes upon coenzyme binding. This knowledge has facilitated the development of novel inhibitors that target NSDHL and suppress epidermal growth factor receptor (EGFR) activity, showing potential as therapeutic agents against NSDHL-related diseases .