Dysregulated cholesterol metabolism in genodermatoses: implications for systemic disease and therapeutic strategies.

Cholesterol plays a critical role in maintaining normal physiological functions, and it is particularly important in skin tissue. Dysregulation of cholesterol metabolism can lead to a spectrum of skin disorders, including ichthyosis, porokeratosis, keratosis follicularis spinulosa decalvans and related diseases. While the pathogenesis of certain genodermatoses of keratinization has been clearly linked to abnormal cholesterol metabolism, known genetic mutations account for only a subset of cases, suggesting additional cholesterol-linked modifiers, suggesting a potential involvement of cholesterol-related pathways. This review summarizes recent advances in understanding genodermatoses of keratinization associated with disrupted cholesterol metabolism and discusses their underlying molecular mechanisms. A better understanding of cholesterol dysregulation may facilitate the identification of novel diagnostic biomarkers and therapeutic targets, providing new opportunities for precision management of inherited keratinization disorders.