Lysophosphatidylcholine acyltransferase 3 (LPCAT3) (LPCAT3)

Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a critical enzyme within the membrane-bound O-acyltransferase (MBOAT) family that facilitates the Lands' cycle of phospholipid remodeling [1: UniProt Q6P1A2]. It specifically catalyzes the incorporation of polyunsaturated fatty acids (PUFAs), particularly arachidonic acid, into lysophosphatidylcholine to form phosphatidylcholine [2: PMID 26412324]. This activity is essential for maintaining cellular membrane composition, fluidity, and the assembly of very-low-density lipoproteins (VLDL) in the liver [3: PMID 27126038, 4: PMID 24231354]. LPCAT3 has emerged as a significant therapeutic target due to its role in ferroptosis, a form of regulated cell death driven by lipid peroxidation; loss of LPCAT3 reduces the abundance of PUFA-containing phospholipids, thereby conferring resistance to ferroptotic stimuli [2: PMID 26412324, 5: PMID 27941786]. In metabolic diseases, LPCAT3 deficiency or inhibition has been shown to impact lipid absorption and systemic triglyceride levels, making it a focus for treating nonalcoholic fatty liver disease (NAFLD) and atherosclerosis [4: PMID 24231354, 6: PMID 25947375]. While no small-molecule drugs are currently FDA-approved, research into antisense oligonucleotides (ASOs) and siRNA targeting LPCAT3 mRNA is active for modulating lipid metabolism and cancer cell sensitivity [5: PMID 27941786, 7: PMID 29540573].

Other names

MBOAT5Membrane bound O-acyltransferase domain containing 5C3orf18OACT5LPSATLysophosphatidylserine acyltransferaseLPCAT3 mRNA

Reduction of LPCAT3 mRNA levels via antisense oligonucleotides or siRNA, or direct inhibition of enzyme activity, to decrease the incorporation of polyunsaturated fatty acids into phospholipids, thereby modulating membrane composition and ferroptosis sensitivity.