Defective targeting of PNPLA1 to lipid droplets causes ichthyosis in ABHD5-syndromic epidermal differentiation disorder.

ABSTRACT: ABHD5-syndromic epidermal differentiation disorder (ABHD5-sEDD; also known as Chanarin-Dorfman syndrome) is a rare autosomal recessive disorder caused by mutations in the α/β-hydrolase domain-containing 5 (ABHD5) gene, leading to systemic accumulation of neutral lipids and ichthyosis due to impaired activation of patatin-like phospholipase domain-containing (PNPLAs) proteins. While ABHD5 is a well-known co-activator of adipose triglyceride lipase (ATGL, also referred to as PNPLA2), its role in epidermal lipid metabolism is incompletely understood. Here, we identify ABHD5 as a key regulator of PNPLA1, an enzyme essential for ω-O-acylceramide (acylCer) synthesis and skin barrier formation. We analyzed seven disease-associated ABHD5 missense mutations and found that they disrupt PNPLA1 locali

SUBMITTER: Schratter M 

PROVIDER: S-EPMC12465037 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature