ABHD5 (abhydrolase domain containing 5) is a multifunctional protein that primarily functions as a coactivator of adipose triglyceride lipase (ATGL) in lipid metabolism and possesses lysophosphatidic acid acyltransferase activity 1. The protein regulates lipolysis by controlling the access of lipases to substrate lipids stored within lipid droplets, normally binding to perilipin 1 until released by PKA-dependent catecholamine stimulation 1. Beyond its canonical lipolytic function, ABHD5 demonstrates proteolytic activity as a serine protease that cleaves HDAC4, producing an N-terminal fragment that inhibits MEF2-dependent gene expression and controls glucose metabolism 2. Additionally, ABHD5 suppresses cancer cell stemness by interacting with DPY30 in the cytoplasm, preventing its nuclear translocation and subsequent SET1A-mediated methylation of YAP and histone H3 3. Recent evidence indicates that PNPLA3(148M) promotes hepatic steatosis by sequestering ABHD5, limiting its availability to activate ATGL-mediated triglyceride hydrolysis 4. Clinically, mutations in ABHD5 cause Chanarin-Dorfman syndrome, a rare autosomal recessive lipid storage disorder characterized by ichthyosis, hepatomegaly, hearing loss, and lipid accumulation in neutrophils 5. ABHD5 deficiency in cardiac tissue leads to heart failure, and reduced ABHD5 levels are observed in failing human hearts 2.