Cytochrome P450 family 4 subfamily F member 22 (CYP4F22)

Cytochrome P450 family 4 subfamily F member 22 (CYP4F22) is a microsomal omega-hydroxylase enzyme that belongs to the cytochrome P450 superfamily, specifically classified as a monooxygenase[4]. It catalyzes the ω-hydroxylation of ultra-long-chain fatty acids (ULCFAs), typically those with carbon chain lengths of 28 or more (C28–C36), prior to their incorporation into acylceramides[2][3][4]. These acylceramides are essential lipids necessary for the formation and maintenance of the epidermal permeability barrier in the stratum corneum, the outermost layer of the skin[2][3][4]. CYP4F22 is a membrane-associated protein located in the endoplasmic reticulum, using molecular oxygen and electrons from NADPH to hydroxylate its fatty acid substrates[2][4]. Loss-of-function mutations in CYP4F22 disrupt acylceramide biosynthesis, causing epidermal barrier defects characterized clinically as autosomal recessive congenital ichthyosis (ARCI), including the lamellar ichthyosis subtype; such defects impair the skin’s water barrier and can lead to severe dehydration and skin pathology[2][3][4]. CYP4F22 is highly expressed in epidermal layers and is genetically and functionally essential for healthy skin barrier physiology[3][4]. No approved drugs are known to specifically target or modulate CYP4F22, and no well-validated small molecule inhibitors or activators are documented in the literature. Mutational analysis of CYP4F22 is used as a diagnostic biomarker for specific types of congenital ichthyosis, and reduced acylceramide levels in the skin serve as a biochemical marker for disease[3][4]. Safety concerns primarily relate to the consequences of impaired skin barrier function due to enzyme deficiency.

Other names

Ultra-long-chain fatty acid omega-hydroxylaseFLJ39501Cytochrome P450 4F22ARCI5INLNELI3CYP4F22cytochrome P450, family 4, subfamily F, polypeptide 22