ABHD17C is a serine hydrolase that functions as a protein depalmitoylase, catalyzing the removal of palmitate from S-acylated cysteine residues on target proteins 1. It removes fatty acyl chains from substrates including N-Ras and PSD95, regulating their subcellular localization and signaling activity 1. ABHD17C is part of a family of ABHD17 isoforms (A, B, C) that share depalmitoylation capacity and operate independently from classical depalmitoylases APT1/2 1. In disease contexts, ABHD17C plays prominent roles in cancer progression. In pancreatic ductal adenocarcinoma, KRAS mutation-driven phosphorylation of ABHD17C promotes depalmitoylation and degradation of ALOX15B, enabling ferroptosis evasion and tumor growth; disrupting ABHD17C/ALOX15B interaction restores ferroptosis sensitivity 2. In lung adenocarcinoma, ABHD17C marks a tumor subtype (C4) associated with epithelial-to-mesenchymal transition, immune evasion, and metastatic potential; ABHD17C knockdown reduces cell proliferation and increases apoptosis 3. ABHD17C also emerges as a prognostic biomarker in pancreatic cancer 4. Additionally, ABHD17C negatively regulates NOD2, an innate immune receptor; inhibiting ABHD17C enhances NOD2 membrane localization and pro-inflammatory signaling, offering therapeutic potential for Crohn's disease-associated NOD2 variants 5. ABHD17C's localization and catalytic activity depend on its own palmitoylation state and endosomal sorting mechanisms 6.