The present invention provides methods of identifying polypeptides that have enzymatic activity associated with nutrient and/or energy homeostasis, and thus, are involved in the development of one or more cardiovascular and metabolic disorders, e.g., cardiovascular disease, obesity, insulin resistance, type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease, and metabolic syndrome. One such method comprises identifying a polypeptide as a member of the adiponutrin family of proteins. As such, the invention is related to the polynucleotides and polypeptides belonging to the adiponutrin family, and provides novel isolated and purified polynucleotides and polypeptides of a novel member of the adiponutrin family, patatin-like phospholipase domain 1 (PNPLA1). Also provided are methods of using the polynucleotides and polypeptides related to or provided by the invention for screening a test compound, e.g., a small molecule, antibody, etc., for the ability of the test compound to detect and/or modulate the activity of one or more members of the adiponutrin family of proteins. The present invention also is directed to novel methods for diagnosing, prognosing, and monitoring the progress of at least one cardiovascular and metabolic disorder using polynucleotides or polypeptides belonging to the adiponutrin family, and/or modulators of one or more members of the adiponutrin family. The present invention is further directed to novel therapeutics and therapeutic targets for the intervention (treatment) and prevention of cardiovascular and metabolic disorders arising from dysregulated energy homeostasis, as related to one or more members of the adiponutrin family of proteins.