Lipin 2 is a phosphatidic acid phosphatase (PAP) responsible for the penultimate 
step of triglyceride synthesis and dephosphorylation of phosphatidic acid (PA) 
to generate diacylglycerol. The lipin family of PA phosphatases is composed of 
lipins 1-3, which are members of the conserved haloacid dehalogenase 
superfamily. Although genetic alteration of LPIN2 in humans is known to cause 
Majeed syndrome, little is known about the biochemical regulation of its PAP 
activity. Here, in an attempt to gain a better general understanding of the 
biochemical nature of lipin 2, we have performed kinetic and phosphorylation 
analyses. We provide evidence that lipin 2, like lipin 1, binds PA via the 
electrostatic hydrogen bond switch mechanism but has a lower rate of catalysis. 
Like lipin 1, lipin 2 is highly phosphorylated, and we identified 15 
phosphosites. However, unlike lipin 1, the phosphorylation of lipin 2 is not 
induced by insulin signaling nor is it sensitive to inhibition of the mammalian 
target of rapamycin. Importantly, phosphorylation of lipin 2 does not negatively 
regulate either membrane binding or PAP activity. This suggests that lipin 2 
functions as a constitutively active PA phosphatase in stark contrast to the 
high degree of phosphorylation-mediated regulation of lipin 1. This knowledge of 
lipin 2 regulation is important for a deeper understanding of how the lipin 
family functions with respect to lipid synthesis and, more generally, as an 
example of how the membrane environment around PA can influence its effector 
proteins.