ABHD17B is a depalmitoylase enzyme that removes palmitate from S-acylated cysteine residues in proteins, regulating their subcellular localization and function 1. The enzyme demonstrates substrate specificity, with confirmed depalmitoylating activity towards multiple proteins including N-Ras, DLG4/PSD95, and NOD2 12. ABHD17B functions as part of a broader family of ABHD17 proteins (A, B, C) that collectively regulate the palmitoylation cycle of membrane-associated proteins, particularly at the plasma membrane 3. The enzyme plays critical roles in cellular processes including protein trafficking, membrane localization, and signal transduction. In disease contexts, ABHD17B has emerged as a potential therapeutic target across multiple conditions. In hepatic stellate cells, ABHD17B depletion promotes cell inactivation and protection from liver fibrosis, suggesting anti-fibrotic properties 4. The enzyme also regulates N-Ras-dependent cancer growth, with selective inhibitors showing promise for treating NRAS-mutant acute myeloid leukemia 3. Additionally, ABHD17B modulates innate immunity by negatively regulating NOD2 function, with inhibition potentially offering therapeutic benefits for Crohn's disease-associated NOD2 variants 2. The enzyme's expression patterns have also been implicated in hepatocellular carcinoma progression and may serve as a biomarker for advanced cirrhosis 56.