Chanarin Dorfman Syndrome (CDS; MIM: 275630) is a rare autosomal recessive disorder, characterized by tri-acylglycerol (TG) accumulation in lipid droplets (LDs) within different tissues including skin, liver, skeletal muscle, bone marrow, eyes, ears, and central nervous system. In CDS, the prevalent and always observed clinical feature is a nonbullous congenital ichthyosiform erythroderma (NCIE). Liver and muscle involvement is detected in more than 80% and 40% of cases, respectively. Neurological symptoms have been reported in almost 30% of affected subjects. The disease is due to mutations in the α/β-hydrolase domain-containing protein 5(ABHD5). This protein can activate both adipose triglyceridelipase (ATGL), thefirstrate-settingenzymeinTG hydrolysis, and PNPLA1, which catalyzes the final step of ὠ-O-acylceramide production.