ABHD16A is a phospholipase that catalyzes the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS), a signaling lipid regulating immunological and neurological processes 1. The enzyme also possesses monoacylglycerol lipase activity with preference for long-chain unsaturated substrates 2. Beyond lipid metabolism, ABHD16A functions as a depalmitoylase that negatively regulates antiviral immunity by catalyzing depalmitoylation of IFITM proteins, thereby reducing their antiviral activity against RNA viruses and hepatitis B virus 34. ABHD16A is localized to the endoplasmic reticulum and highly expressed in the cerebellum, where it regulates lysophosphatidylserine levels 5. In tumor microenvironments, ABHD16A-generated lysophosphatidylserine inhibits type 1 innate lymphoid cell activation via GPR34 receptor signaling, suppressing antitumor immunity 6. Pathologically, mutations in ABHD16A cause spastic paraplegia 86, an autosomal recessive disorder. ABHD16A activity is regulated by ubiquitin-mediated degradation 7 and represents a therapeutic target for viral infections and cancer immunotherapy through selective inhibition 8.