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Molecular players and dynamic protein-protein interactions PNPLA2 is activated by co-regulator alpha/beta hydrolase domain-containing protein 5 PNPLA2, the rate limiting enzyme for TAG hydrolysis was initially identified independently in 2004 by the groups of Gross (21), Zechner (17) and Sul (28), with subsequent work from the Zechner group demonstrating PNPLA2 as the rate limiting step in TAG hydrolysis in vivo (29)