Abhydrolase domain-containing protein 5 (ABHD5) (ABHD5)

Abhydrolase domain-containing protein 5 (ABHD5), also known as CGI-58, is a critical regulatory protein in lipid metabolism that functions as the primary co-activator of adipose triglyceride lipase (ATGL) [UniProt: Q8WUW4]. Although it belongs to the alpha/beta hydrolase fold family, it lacks the catalytic triad required for independent lipase activity and instead acts by binding to ATGL to stimulate its enzymatic rate by up to 20-fold [PubMed: 16415873]. In resting cells, ABHD5 is sequestered on the surface of lipid droplets by perilipin 1 (PLIN1); upon hormonal stimulation and subsequent phosphorylation of PLIN1, ABHD5 is released to activate ATGL and initiate lipolysis [PubMed: 25159611]. Mutations in the ABHD5 gene are the underlying cause of Chanarin-Dorfman syndrome, a rare autosomal recessive disorder characterized by systemic triglyceride accumulation and skin ichthyosis [NCBI Gene: 51099]. Due to its central role in controlling the mobilization of stored fats, ABHD5 is a significant therapeutic target for metabolic diseases, including non-alcoholic fatty liver disease (NAFLD) and obesity [PubMed: 30104304]. Modulating ABHD5 activity offers a potential pathway to regulate lipid levels and improve insulin sensitivity in patients with metabolic syndrome.

Other names

CGI-58Comparative gene identification 58NCIE2IECN21-acylglycerol-3-phosphate O-acyltransferase ABHD5

Co-activation of adipose triglyceride lipase (ATGL) through direct protein-protein interaction, facilitating the hydrolysis of triacylglycerols into diacylglycerols and free fatty acids [PubMed: 16415873].