ABHD17A (abhydrolase domain containing 17A) is a depalmitoylase enzyme that removes palmitate groups from S-acylated cysteine residues in proteins, thereby regulating protein localization and function. The enzyme demonstrates depalmitoylating activity toward multiple protein targets including NRAS, DLG4/PSD95, and NLRP3 1. ABHD17A plays a crucial role in immune regulation by depalmitoylating NLRP3, which modulates inflammasome activation and inflammatory responses 1. Additionally, ABHD17A exhibits an unconventional function by downregulating another depalmitoylase, ABHD16A, thereby increasing S-palmitoylation and antiviral activity of IFITM1 2. In cancer biology, ABHD17A contributes to metabolic regulation by modulating SCAP S-acylation, affecting cholesterol biosynthesis in hepatocellular carcinoma 3. The enzyme also influences cellular signaling pathways, including calcineurin phosphatase targeting to the phosphatidylinositol 4-kinase complex at the plasma membrane 4 and Rap2b localization in colorectal cancer metastasis 5. Clinical significance includes potential associations with coronary artery disease and type 2 diabetes mellitus 6, and involvement in immune responses following viral infections 7. These diverse functions position ABHD17A as a critical regulator of protein palmitoylation with implications for inflammation, cancer, and metabolic diseases.