Acyl-protein thioesterase 1 (APT1)

Acyl-protein thioesterase 1 (APT1, encoded by LYPLA1) is an enzyme of the alpha/beta hydrolase superfamily that exhibits both depalmitoylating and lysophospholipase activities[1]. It catalyzes the removal of palmitate and other fatty acyl groups from S-acylated cysteine residues on substrate proteins—a reversible posttranslational modification called S-palmitoylation[1][4]. By regulating this cycle, APT1 controls protein membrane association, trafficking, and downstream signaling, affecting pathways such as Ras localization, G protein signaling, and autophagy[1][2][4]. In neurons, APT1 has a role in dendritic spine morphogenesis and synaptic function[4]. Dysregulation of LYPLA1/APT1 is implicated in diseases including cancer, neurodegeneration, and metabolic disorders, and its inhibition has been shown to impact apoptosis (e.g., in leukemia cells) and reduce proliferation and migration in certain cancer types[5][7]. Research inhibitors of APT1 are under development and represent potential therapeutic strategies; however, broad effects on protein palmitoylation underscore the need for careful assessment of safety and specificity[7][2][4].

Other names

LYPLA1Lysophospholipase 1Palmitoyl-protein hydrolaseAcyl-protein thioesterase 1APT1LPL1hAPT1LPL-ILysoPLA ILysophospholipase ILysophospholipid-specific lysophospholipase

Enzyme inhibitors of APT1 increase global protein palmitoylation by inhibiting depalmitoylation[7]. APT1 targeting drugs/interventions can modulate apoptosis by affecting palmitoylation status of death receptors and signaling proteins[7].