Abhd17b, an α/β-hydrolase domain-containing protein, functions as a depalmitoylase. It is involved in pathways related to protein palmitoylation/depalmitoylation cycles, which play crucial roles in protein subcellular trafficking and function. These cycles are important in various biological processes and disease-related mechanisms [1,3,4,5].

In hepatic stellate cells (HSCs), the nuclear receptor Nur77 transcriptionally activates Abhd17b expression to inhibit hexokinase 1 (HK1) palmitoylation, thus attenuating HK1 release from HSCs and potentially affecting hepatocellular carcinoma (HCC) progression [1].

In primary human HSC myofibroblasts, depletion of Abhd17b promotes HSC inactivation, characterized by reduced COL1A1 and ACTA2 expression and lipid droplet accumulation. Mice deficient in Abhd17b are protected from fibrosis in in vivo liver injury, suggesting that Abhd17b may promote fibrosis through non-depalmitoylation-dependent pathways, such as interacting with MYO1B to modulate gene expression and HSC migration [2].

In engineered cell lines, Abhd17b, along with other ABHD17 isoforms, is identified as an acyl protein thioesterase responsible for deacylating NOD2, an intracellular innate immune receptor. Inhibiting ABHD17 isoforms increases the plasma membrane localization of NOD2 and a subset of Crohn's disease-associated variants, enhancing NOD2 activity [3,4].

In human acute myeloid leukemia (AML) cells, a selective inhibitor of ABHD17 family (ABD957) impairs N-Ras depalmitoylation, N-Ras signaling, and the growth of NRAS-mutant AML cells [5].

In summary, Abhd17b plays essential roles in multiple biological processes and disease conditions. Studies using gene-knockout models, such as Abhd17b-deficient mice, have revealed its functions in liver fibrosis, innate immune regulation, and cancer-related signaling pathways. These findings highlight the potential of targeting Abhd17b as a therapeutic strategy for liver fibrosis, Crohn's disease, and NRAS-mutant cancers [1,2,3,4,5].