Lysophospholipase 1 (LYPLA1) (LYPLA1)

Lysophospholipase 1 (LYPLA1), also known as Acyl-protein thioesterase 1 (APT1), is a cytosolic serine hydrolase that plays a critical role in the dynamic regulation of protein palmitoylation [1]. It specifically catalyzes the removal of palmitate groups from cysteine residues on various signaling proteins, such as Ras GTPases and G-protein alpha subunits [2]. By regulating the palmitoylation cycle, LYPLA1 controls the membrane localization and signaling activity of these proteins [3]. In the context of disease, LYPLA1 is often implicated in cancer, particularly those driven by oncogenic Ras mutations, where its inhibition can disrupt Ras localization and suppress downstream signaling [4]. While most current research focuses on small molecule inhibitors of the LYPLA1 protein, the LYPLA1 mRNA represents a potential target for RNA-interference (RNAi) or antisense oligonucleotide (ASO) therapies aimed at reducing enzyme expression [5]. Therapeutic strategies targeting LYPLA1 aim to restore normal signaling homeostasis in hyperactive pathways [1]. This enzyme is also involved in the hydrolysis of lysophospholipids, contributing to broader lipid metabolism within the cell [1]. Overall, LYPLA1 serves as a pivotal node in cellular signaling and a promising candidate for targeted therapy in oncology and metabolic disorders [4].

Other names

Acyl-protein thioesterase 1APT1LPL1hLPL1APT-1

The primary mechanism of action for targeting LYPLA1 involves the inhibition of its thioesterase activity, which prevents the depalmitoylation of proteins like H-Ras and N-Ras. This leads to the accumulation of palmitoylated proteins on endomembranes and their subsequent mislocalization, effectively quenching their ability to participate in plasma membrane-associated signaling cascades [2, 4]. Targeting the LYPLA1 mRNA via RNA interference (RNAi) achieves a similar effect by reducing the total cellular pool of the enzyme, thereby slowing the rate of protein deacylation [5].