LIPN encodes an epidermal lipase with a critical role in the final stages of keratinocyte differentiation. The protein contains an alpha/beta hydrolase fold and possesses genuine lipase active-site residues, suggesting authentic lipase activity in lipid metabolism within the outermost differentiated epidermal layers. LIPN is exclusively expressed in the epidermis and becomes strongly induced as keratinocytes differentiate 1. The enzyme localizes to the extracellular region and is implicated in cornification and lipoprotein lipid processing. LIPN mutations cause autosomal recessive congenital ichthyosis (ARCI), a rare disorder of epidermal cornification characterized by dry, scaly skin resulting from defective lipid metabolism and barrier function 1. Pathogenic variants in LIPN account for 2–5% of ARCI cases across diverse populations 2, 3. The enzyme is thought to participate in processing ω-hydroxyceramides within the corneocyte lipid envelope, which is essential for maintaining the epidermal barrier 4. A genome-wide association study in Chinese women identified LIPN among genes enriched for lipase and lipoprotein lipase activity in the context of gestational diabetes mellitus, suggesting a broader metabolic role beyond skin physiology 5. Currently, no disease-modifying therapies specifically target LIPN, though understanding its mechanism may inform future treatment strategies for ichthyosis and related keratinization disorders.