biostudies-literatureUnknownTeskey GNIDDK NIH HHSNHLBI NIH HHSThe storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. α/β hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD bound protein that functions as a co-activator of Patatin Like Phospholipase Domain Containing 2 (PNPLA2; also known as Adipose triglyceride lipase, ATGL) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). We previously demonstrated that ABHD5 interacted with PNPLA3, a closely related family member to PNPLA2. Importantly, a common missense variant in PNPLA3 (I148M) is the greatest genetic risk factor for MASLD. PNPLA3 148M functions to sequesbioRxiv : the preprint server for biology2024.10.03.616525https://www.ebi.ac.uk/biostudies/studies/S-EPMC11601262biostudies-literatureLipid droplet targeting of ABHD5 and PNPLA3 I148M is required to promote liver steatosis.PMC11601262P30 DK092926T32 HL120822R01 DK126743Butcko AJHuang YMKelly CVMottillo EPTiwari NGranneman JGPerfield JWTeskey GKumar AYadav AfalseLipid droplet targeting of ABHD5 and PNPLA3 I148M is required to promote liver steatosis.The storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. α/β hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD bound protein that functions as a co-activator of Patatin Like Phospholipase Domain Containing 2 (PNPLA2; also known as Adipose triglyceride lipase, ATGL) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). We previously demonstrated that ABHD5 interacted with PNPLA3, a closely related family member to PNPLA2. Importantly, a common missense variant in PNPLA3 (I148M) is the greatest genetic risk factor for MASLD. PNPLA3 148M functions to seques2024-01-01T00:00:00Z2024 Nov2026-04-16T03:28:15.052Z2025-04-06T01:56:07.792ZS-EPMC116012623960554110.1101/2024.10.03.616525